BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.展开更多
Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME...Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.展开更多
Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor pro...Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors.CASE SUMMARY We report on three BPDCN cases,all characterized by skin nodules and examined by histology,immunohistochemical detection,in situ hybridization for Epstein-Barr virus,and follow-up.We also review the relevant literature.All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA.Two patients had bone marrow involvement.Chemotherapy is the main treatment for BPDCN,but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy.Case 1 survived for 7 mo,case 2 for 17 mo,and case 3 for 9 mo.CONCLUSION An accurate pathological diagnosis is a precondition for treatment,and the diagnosis of BPDCN should be based on a combination of clinical symptoms,pathological characteristics,immunophenotype,and other auxiliary examinations.It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists.Case 2 survived significantly longer than the other two cases,suggesting that the treatment received by case 2 was more effective.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,ly...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.展开更多
We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin m...We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions a...BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.展开更多
Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent orunregulated proinflammatory cytokine responses are associated with severe disease outcomes. ...Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent orunregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested thatmonocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that uponphagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turnmediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF.Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrinmediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present studydescribes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells.These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which maycontribute to tissue damage and severe disease.展开更多
Appropriate in vivo control of plasmacytoid dendritic cell (pDC) recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the ...Appropriate in vivo control of plasmacytoid dendritic cell (pDC) recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the outcome of viral infection is the production of high levels of type I interferon by pDCs. In particular, recent research findings showed that pDCs not only shape the nature of innate resistance, but are also responsible for the successful transition from innate to adaptive immunity for viral resistance. In addition, pDCs can differentiate into antigen presenting cells that may regulate tolerance to a given pathogen. Importantly, in a series of recent clinical studies, pDCs appeared to be defective in number and function in conditions of chronic viral diseases such as infected with HIV-1, HBV or HCV. pDC-associated clinical antiviral therapy is also emerging. This review describes research findings exatnining the functional and antiviral properties of in vivo pDC plasticity. Cellular & Molecular Immunology. 2005;2(6):411- 417.展开更多
Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response ...Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response to nu-cleic acids derived from virus,bacteria or dead cells.PDCs selectively express endosomal Toll-like receptor(TLR)7 and TLR9,which sense viral RNA and DNA re-spectively.Following type I IFN and cytokine responses,pDCs differentiate into antigen presenting cells and ac-quire the ability to regulate T cell-mediated adaptive immunity.The functions of pDCs have been implicated not only in antiviral innate immunity but also in immune tolerance,inflammation and tumor microenvironments.In this review,we will focus on TLR7/9 signaling and their regulation by pDC-specific receptors.展开更多
Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive....Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive.Plasmacytoid dendritic cells(pDCs),which play a regulatory role in allergic asthma,were shown to be deficient in neonatal mice.We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model.Adoptive transfer of pDCs or administration of IFN-αto neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1−/−mice.Similarly,adult mice developed more severe allergic inflammation when pDCs were depleted.The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20,GM-CSF,and IL-33,which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway.In asthmatic patients,the percentage of pDCs and the level of IFN-αwere lower in children than in adults.These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergeninduced allergic airway inflammation.展开更多
Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid den...Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.展开更多
Arsenic trioxide(As2O3)is recently found to have therapeutic potential in systemic sclerosis(SSc),a life-threatening multi-system fibrosing autoimmune disease with type I interferon(IFN-I)signature.Chronically activat...Arsenic trioxide(As2O3)is recently found to have therapeutic potential in systemic sclerosis(SSc),a life-threatening multi-system fibrosing autoimmune disease with type I interferon(IFN-I)signature.Chronically activated plasmacytoid dendritic cells(pDCs)are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc.In this study,we showed that high concentrations of As2O3 induced apoptosis of pDCs via mitochondrial pathway with increased BAX/BCL-2 ratio,while independent of reactive oxygen species generation.Notably,at clinical relevant concentrations,As2O3 preferentially inhibited IFN-αsecretion as compared to other cytokines such as TNF-α,probably due to potent down-regulation of the total protein and mRNA expression,as well as phosphorylation of the interferon regulatory factor7(IRF7).In addition,As2O3 induced a suppressive phenotype,and in combination with cytokine inhibition,it down-regulated pDCs’capacity to induce CD4+T cell proliferation,Thl/Th22 polarization,and B cell differentiation towards plasmablasts.Moreover,chronically activated pDCs from SSc patients were not resistant to the selective IFN-αinhibition,and regulatory phenotype induced by As2O3.Collectively,our data suggest that As2O3 could target pDCs and exert its treatment efficacy in SSc,and more autoimmune disorders with IFN-I signature.展开更多
Plasmacytoid dendritic cells(pDCs)are decreased in number and are functionally impaired in HIV act reasons for pDCs depletion are still unknown.It was recently reported that pDCs can be divided into two functionally d...Plasmacytoid dendritic cells(pDCs)are decreased in number and are functionally impaired in HIV act reasons for pDCs depletion are still unknown.It was recently reported that pDCs can be divided into two functionally distinct populations based on their CD2 expression level.To determine how the CD2high and CD2^(low) populations are affected by HIV infection,we analyzed their frequencies in the peripheral blood of HIV-infected subjects and healthy controls.We found that the CD2^(low) pDC subset was preferentially depleted in infected individuals.The frequency of CD2^(low) pDCs correlated with the CD41 T-cell count but not with the plasma viral load.This finding furthers our understanding of the causes and consequences of pDC depletion during HIV infection.展开更多
Introduction:Mature plasmacytoid dendritic cells(pDCs)proliferation associated with myeloid neoplasms(MPDMN)are recognized as a neoplasm related to fully differentiated pDCs.Although it has been reported for many year...Introduction:Mature plasmacytoid dendritic cells(pDCs)proliferation associated with myeloid neoplasms(MPDMN)are recognized as a neoplasm related to fully differentiated pDCs.Although it has been reported for many years,the genomic landscape of MPDMN is poorly understood.Methods:We reported two patients who developed acute myeloid leukemia(French-American-British M5 subtype)coexisted with immunophenotypically mature pDCs proliferation,which fit the diagnosis of MPDMN.We sorted pDCs from myeloid blasts by flow cytometry and performed whole-exome sequencing and RNA sequencing of the two cell populations,respectively.Results:The immunophenotypes of pDCs in both patients were positive for CD123bri,HLA-DR,CD4,CD303,CD304,and negative for CD56,CD34,CD117,and TdT.The variant allele frequency of gene mutations in myeloid blasts and pDCs were similar.The expression data showed myeloid blasts clustered tightly with hematopoietic stem cells,and pDCs from patients clustered tightly with granulocyte-monocyte progenitors/common myeloid progenitor,rather than with pDCs from the GEO platform.Conclusion:Our study suggested that pDCs derived from the leukemic clone,evidenced by a shared mutation profile and similar transcriptional signatures between pDCs and concurrent myeloid blasts.展开更多
Acute-on-chronic liver failure (ACLF) is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The ...Acute-on-chronic liver failure (ACLF) is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells (mDCs) and the efficacy of methylprednisolone (MP) treatment for hepatitis B virus (H BV)-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical (CM) management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.展开更多
The dendritic cell system contains conventional dendritic cells(DCs)and plasmacytoid pre-dendritic cells (pDCs).Both DCs and pDCs are bone marrow derived cells.Although the common functions of DCs are antigen-processi...The dendritic cell system contains conventional dendritic cells(DCs)and plasmacytoid pre-dendritic cells (pDCs).Both DCs and pDCs are bone marrow derived cells.Although the common functions of DCs are antigen-processing and T-lymphocyte activation,they differ in surface markers,migratory patterns,and cytokine output.These differences can determine the fate of the T cells they activate.Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively.The original concept that all DCs were of myeloid origin was questioned by several recent studies,which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors.Moreover,it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic pro- genitors regardless of their myeloid-or lymphoid-origin.These findings suggest an early developmental flexibility of precursors for DCs and pDCs.This review summarizes some recent observations on the deve- lopment of DC system in both human and mouse.Cellular & Molecular Immunology.2004;1(2):112-118.展开更多
Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobu...Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.展开更多
Background Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim ...Background Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation. Methods Immunofluorescent flow cytometry was used to classify white blood cells (WBCs), the levels of mononuclear cells and DCs (including the dominant subpopulations, plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0, 1, 7, and 28 days and 1 year after kidney transplantation in 33 patients. In addition, the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery. Fifteen healthy volunteers served as normal controls. Patients were undertaking hemodialysis owing to uremia before surgery. Results The total number of DCs, pDC, and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P 〈0.05). Peripheral DCs suddenly decreased at the end of day 1, then gradually increased through day 28 but remained below normal levels. After 1 year, levels were higher than before surgery but lower than normal. The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P 〈0.005). There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection. Conclusion The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state, and predicting rejection and reasonably adjusting immunosuppressants.展开更多
Understanding the defense mechanisms of the host of an organism is important for infection control.In previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mono...Understanding the defense mechanisms of the host of an organism is important for infection control.In previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus(VZV).Here,we investigated what kind of cell(s)and which signal molecule(s)are involved in IFN-a production.Using cell isolation and ELISA,we found that plasmacytoid dendritic cells(pDCs)were responsible for IFN-a production during VZV infection.We also found that Toll-like receptor 9(TLR9)was involved in VZV-induced IFN-a production because inhibitory CpG oligodeoxynucleotide inhibited IFN-a production.UV-inactivated VZV-induced IFN-a production was lower than that of active VZV,indicating another TLR9-independent pathway.Further studies demonstrated that double-stranded RNA-dependent protein kinase,but not DNA-dependent protein kinase was involved in VZV-induced IFN-a production.Together,these results suggest that pDCs play an important role in IFN-a production during VZV infection through TLR9-dependent and-independent pathways.展开更多
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.
基金supported by grants from the China Postdoctoral Science Foundation(Grant No.2022M712880)the Program of the Major Research Plan of the National Natural Science Foundation of China(Grant No.91942314)the National Natural Science Foundation of China(Grant No.82001659).
文摘Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.
基金the National NaOiral Science Foundation of China(No.81460030,81770221).
文摘Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors.CASE SUMMARY We report on three BPDCN cases,all characterized by skin nodules and examined by histology,immunohistochemical detection,in situ hybridization for Epstein-Barr virus,and follow-up.We also review the relevant literature.All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA.Two patients had bone marrow involvement.Chemotherapy is the main treatment for BPDCN,but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy.Case 1 survived for 7 mo,case 2 for 17 mo,and case 3 for 9 mo.CONCLUSION An accurate pathological diagnosis is a precondition for treatment,and the diagnosis of BPDCN should be based on a combination of clinical symptoms,pathological characteristics,immunophenotype,and other auxiliary examinations.It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists.Case 2 survived significantly longer than the other two cases,suggesting that the treatment received by case 2 was more effective.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.
基金Supported by The Chongqing Health Commission and Science and Technology Bureau,No.2023MSXM060.
文摘We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.
基金Supported by The National Key Research and Development Programs of China,No.2022YFC2603801Maternal and Child Health Project of Jiangsu Province,No.F201717+1 种基金Doctor Project of Affiliated Hospital of Jiangsu University,No.jdfyrc2019003Clinical and Virology Study of 2019-ncov Infection in Patients with Moderate to Severe Psoriasis,No.Jdfyxgzx005.
文摘BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.
文摘Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent orunregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested thatmonocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that uponphagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turnmediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF.Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrinmediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present studydescribes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells.These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which maycontribute to tissue damage and severe disease.
基金the National Outstanding Youth Foundation of China(No.30525042) National Key Basic Research Program of China(No.2001CB51003).
文摘Appropriate in vivo control of plasmacytoid dendritic cell (pDC) recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the outcome of viral infection is the production of high levels of type I interferon by pDCs. In particular, recent research findings showed that pDCs not only shape the nature of innate resistance, but are also responsible for the successful transition from innate to adaptive immunity for viral resistance. In addition, pDCs can differentiate into antigen presenting cells that may regulate tolerance to a given pathogen. Importantly, in a series of recent clinical studies, pDCs appeared to be defective in number and function in conditions of chronic viral diseases such as infected with HIV-1, HBV or HCV. pDC-associated clinical antiviral therapy is also emerging. This review describes research findings exatnining the functional and antiviral properties of in vivo pDC plasticity. Cellular & Molecular Immunology. 2005;2(6):411- 417.
文摘Plasmacytoid dendritic cells(pDCs),also known as type I interferon(IFN)-producing cells,are specialized immune cells characterized by their extraordinary capabilities of mounting rapid and massive type I IFN response to nu-cleic acids derived from virus,bacteria or dead cells.PDCs selectively express endosomal Toll-like receptor(TLR)7 and TLR9,which sense viral RNA and DNA re-spectively.Following type I IFN and cytokine responses,pDCs differentiate into antigen presenting cells and ac-quire the ability to regulate T cell-mediated adaptive immunity.The functions of pDCs have been implicated not only in antiviral innate immunity but also in immune tolerance,inflammation and tumor microenvironments.In this review,we will focus on TLR7/9 signaling and their regulation by pDC-specific receptors.
基金by grants 91542103 and 31770994 from the National Natural Science Foundation of China(to J.H.)grant 2015CFB620 from the Natural Science Foundation of Hubei Province(to J.H.).
文摘Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive.Plasmacytoid dendritic cells(pDCs),which play a regulatory role in allergic asthma,were shown to be deficient in neonatal mice.We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model.Adoptive transfer of pDCs or administration of IFN-αto neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1−/−mice.Similarly,adult mice developed more severe allergic inflammation when pDCs were depleted.The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20,GM-CSF,and IL-33,which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway.In asthmatic patients,the percentage of pDCs and the level of IFN-αwere lower in children than in adults.These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergeninduced allergic airway inflammation.
基金supported by grants from the National Natural Science Foundation of China(No:81870462 and 81470990 to F.Ding,No:91642112 to R.H.,and No:31600715 to Y.L.L.)The Science and Technology Commission of Shanghai Municipality(No:18140903300 to R.H.,No:17441904200 and 19441909300 to F.D.)+5 种基金Shanghai Ninth People’s Hospital Clinical Research Program(No:JYU007 to F.D.)Shanghai Ninth People's Hospital MDT Program(2017-1-019 to F.D.)Major Special Projects of the Ministry of Science and Technology(2018ZX10302207 to Y.L.L.)Development Project of Shanghai Peak Disciplines-Integrative Medicine(20180101 to Y.L.L.)Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine(BXJ201730 to B.D.)Fundamental Research Program Funding of Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine(JYZZ082B to B.D.).
文摘Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.
基金China Scholarship Council for financial support(CSC No.201606320257,China)
文摘Arsenic trioxide(As2O3)is recently found to have therapeutic potential in systemic sclerosis(SSc),a life-threatening multi-system fibrosing autoimmune disease with type I interferon(IFN-I)signature.Chronically activated plasmacytoid dendritic cells(pDCs)are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc.In this study,we showed that high concentrations of As2O3 induced apoptosis of pDCs via mitochondrial pathway with increased BAX/BCL-2 ratio,while independent of reactive oxygen species generation.Notably,at clinical relevant concentrations,As2O3 preferentially inhibited IFN-αsecretion as compared to other cytokines such as TNF-α,probably due to potent down-regulation of the total protein and mRNA expression,as well as phosphorylation of the interferon regulatory factor7(IRF7).In addition,As2O3 induced a suppressive phenotype,and in combination with cytokine inhibition,it down-regulated pDCs’capacity to induce CD4+T cell proliferation,Thl/Th22 polarization,and B cell differentiation towards plasmablasts.Moreover,chronically activated pDCs from SSc patients were not resistant to the selective IFN-αinhibition,and regulatory phenotype induced by As2O3.Collectively,our data suggest that As2O3 could target pDCs and exert its treatment efficacy in SSc,and more autoimmune disorders with IFN-I signature.
基金supported in part by grants from the National Natural Science Foundation of China 30872365(LZ)the Beijing Municipal of Science and Technology Major Project D09050703590901the National Key Technologies R&DProgram for the 11th Five-Year Plan 2008ZX10001-001 and 2008ZX10001-006(HW).
文摘Plasmacytoid dendritic cells(pDCs)are decreased in number and are functionally impaired in HIV act reasons for pDCs depletion are still unknown.It was recently reported that pDCs can be divided into two functionally distinct populations based on their CD2 expression level.To determine how the CD2high and CD2^(low) populations are affected by HIV infection,we analyzed their frequencies in the peripheral blood of HIV-infected subjects and healthy controls.We found that the CD2^(low) pDC subset was preferentially depleted in infected individuals.The frequency of CD2^(low) pDCs correlated with the CD41 T-cell count but not with the plasma viral load.This finding furthers our understanding of the causes and consequences of pDC depletion during HIV infection.
基金was supported in part by State Key Program of National Natural Science of China(81830005)J.W.,National Natural Science Foundation of China(81770181)+3 种基金J.W.,National Key Research and Development Program of China(2019YFC0840605)Y.M.,Tianjin Natural Science Foundation(18JCZDJC45000)H.W.,CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B-084)H.W.Funders had no role in the study design,analyses,or decision to publish.
文摘Introduction:Mature plasmacytoid dendritic cells(pDCs)proliferation associated with myeloid neoplasms(MPDMN)are recognized as a neoplasm related to fully differentiated pDCs.Although it has been reported for many years,the genomic landscape of MPDMN is poorly understood.Methods:We reported two patients who developed acute myeloid leukemia(French-American-British M5 subtype)coexisted with immunophenotypically mature pDCs proliferation,which fit the diagnosis of MPDMN.We sorted pDCs from myeloid blasts by flow cytometry and performed whole-exome sequencing and RNA sequencing of the two cell populations,respectively.Results:The immunophenotypes of pDCs in both patients were positive for CD123bri,HLA-DR,CD4,CD303,CD304,and negative for CD56,CD34,CD117,and TdT.The variant allele frequency of gene mutations in myeloid blasts and pDCs were similar.The expression data showed myeloid blasts clustered tightly with hematopoietic stem cells,and pDCs from patients clustered tightly with granulocyte-monocyte progenitors/common myeloid progenitor,rather than with pDCs from the GEO platform.Conclusion:Our study suggested that pDCs derived from the leukemic clone,evidenced by a shared mutation profile and similar transcriptional signatures between pDCs and concurrent myeloid blasts.
基金ACKNOWLEDGEMENTS This study is supported by the National Natural Science Foundation of China (Nos. 30801039 and 81072424) and the major projects of viral hepatitis from Beijing Municipal Science and Technology Commission (No. H020920020890). We thank the volunteers who generously participated in this study.
文摘Acute-on-chronic liver failure (ACLF) is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells (mDCs) and the efficacy of methylprednisolone (MP) treatment for hepatitis B virus (H BV)-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical (CM) management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.
文摘The dendritic cell system contains conventional dendritic cells(DCs)and plasmacytoid pre-dendritic cells (pDCs).Both DCs and pDCs are bone marrow derived cells.Although the common functions of DCs are antigen-processing and T-lymphocyte activation,they differ in surface markers,migratory patterns,and cytokine output.These differences can determine the fate of the T cells they activate.Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively.The original concept that all DCs were of myeloid origin was questioned by several recent studies,which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors.Moreover,it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic pro- genitors regardless of their myeloid-or lymphoid-origin.These findings suggest an early developmental flexibility of precursors for DCs and pDCs.This review summarizes some recent observations on the deve- lopment of DC system in both human and mouse.Cellular & Molecular Immunology.2004;1(2):112-118.
文摘Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.
基金The study was supported by the National Basic Research Program of China (973 Project) (No. 2009CB522400) and the National Natural Science Foundation of China (No. 30772170).Acknowledgement: The authors wish to thank Bi Rumei, a technician from the Urological Department of Beijing Friendship Hospital, The Capital Medical University, for her support and help in data analysis.
文摘Background Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation. Methods Immunofluorescent flow cytometry was used to classify white blood cells (WBCs), the levels of mononuclear cells and DCs (including the dominant subpopulations, plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0, 1, 7, and 28 days and 1 year after kidney transplantation in 33 patients. In addition, the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery. Fifteen healthy volunteers served as normal controls. Patients were undertaking hemodialysis owing to uremia before surgery. Results The total number of DCs, pDC, and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P 〈0.05). Peripheral DCs suddenly decreased at the end of day 1, then gradually increased through day 28 but remained below normal levels. After 1 year, levels were higher than before surgery but lower than normal. The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P 〈0.005). There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection. Conclusion The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state, and predicting rejection and reasonably adjusting immunosuppressants.
基金grants NSC 94-2314-B-182A-101(HR Yu)NSC 98-2314-B-182A-004-MY3(H R Yu)from the National Science Council,Taiwan.
文摘Understanding the defense mechanisms of the host of an organism is important for infection control.In previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus(VZV).Here,we investigated what kind of cell(s)and which signal molecule(s)are involved in IFN-a production.Using cell isolation and ELISA,we found that plasmacytoid dendritic cells(pDCs)were responsible for IFN-a production during VZV infection.We also found that Toll-like receptor 9(TLR9)was involved in VZV-induced IFN-a production because inhibitory CpG oligodeoxynucleotide inhibited IFN-a production.UV-inactivated VZV-induced IFN-a production was lower than that of active VZV,indicating another TLR9-independent pathway.Further studies demonstrated that double-stranded RNA-dependent protein kinase,but not DNA-dependent protein kinase was involved in VZV-induced IFN-a production.Together,these results suggest that pDCs play an important role in IFN-a production during VZV infection through TLR9-dependent and-independent pathways.