Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

The current role of dendritic cells in the progression and treatment of colorectal cancer

Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer-related deaths worldwide.Dendritic cells(DCs)constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses.As a crucial component of the immune system,DCs have a pivotal role in the pathogenesis and clinical treatment of CRC.DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response.However,the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment.This review systematically elucidates the specific characteristics and functions of different DC subsets,as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment.Moreover,how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed,which will provide new perspectives and approaches for immunotherapy in patients with CRC.

Blastic plasmacytoid dendritic cell neoplasm:Two case reports

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.

Human BDCA2^＋CD123^＋CD56^＋ dendritic cells （DCs） related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset

Dendritic cells （DCs） comprise two functionally distinct subsets： plasmacytoid DCs （pDCs） and myeloid DCs （mDCs）. pDCs are specialized in rapid and massive se- cretion of type I interferon （IFN-I） in response to nucleic acids through Toll like receptor （TLR）-7 or TLR-9. In this report, we characterized a CD56^＋ DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56^＋ DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56^＋ DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naive T cells without prior activation. These data suggest that the CD56^＋ DCs represent a novel mDC subset mixed with some pDC features. A CD4^＋CD56^＋ hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm （BPDCN） due to its expression of characteristic molecules of pDCs.However, we demonstrated that BPDCN is closer to CD56^＋ DCs than pDCs by global gene-expression pro- filing. Thus, we propose that the CD4^＋CD56^＋ neoplasm may be a tumor counterpart of CD56^＋ mDCs but not pDCs.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma

Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.

Overall clinical course of indeterminate dendritic cell tumor patients without skin lesions:A rare case report

BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

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.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

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.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

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.

Flow cytometry assay of myeloid dendritic cells (mDCs)in peripheral blood during acute hepatitis C:Possible pathogenetic mechanisms

AIM： To asses the expression of myeloid dendritic cells （CD11c＋） subset during acute HCV hepatitis and its possible involvement in natural history of the infection.METHODS： We enrolled 11 patients with acute hepatitis C （AHC） （Group A）, 10 patients with acute hepatitis A （AHA） （as infective control-Group B） and 10 healthy donors （group C） in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells （mDCs） to understand the possible role and differences during acute hepatitis.RESULTS： Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count （z=-2.37, P〈0.05） and percentage （z=-2.30; P〈 0.05） as compared with AHA. On the contrary, The remaining three patients of the group A had a higher mDCs number and percentage as occur in group B. Interestingly, after six months, those patients did not show any increase of mDCs subset were chronically infected, while the three subjects with an increase of peripheral mDCs, as in HAV acute infection, resolved the illness.CONCLUSION： The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection.

3D Collagen Gels:A Promising Platform for Dendritic Cell Culture in Biomaterials Research

The three-dimensional(3D)cell culture system has garnered significant attention in recent years as a means of studying cell behavior and tissue development,as opposed to traditional two-dimensional cultures.These systems can induce specific cell reactions,promote specific tissue functions,and serve as valuable tools for research in tissue engineering,regenerative medicine,and drug discovery.This paper discusses current developments in the field of three-dimensional cell culture and the potential applications of 3D type 1 collagen gels to enhance the growth and maturation of dendritic cells.

Study on mechanism of increased allergenicity induced by Ara h 3 from roasted peanut using bone marrow-derived dendritic cells

Little information was so far available about allergenic mechanism of the roasted peanut allergens during initial stages of allergy.The purpose of this study was to determine the influence of roasting(150℃,20 min)on biochemical and biological properties of Ara h 3,a major peanut allergen.Allergenicity of roasted peanut emulsion to mice,differences in uptakes between Ara h 3 purified from raw peanuts(named as Ara h 3-Raw)and that purified from roasted peanuts(named as Ara h 3-Roasted)by bone marrow-derived dendritic cells(BMDCs)and the implication of cell surface receptors involving in uptake,and changes in glycosylation and structure of Ara h 3 after roasting were analyzed in this study.This study suggested that roasting increased allergenicity of peanut to BALB/c mice.Maillard reaction and structural changes of Ara h 3 induced by roasting significantly altered the uptake of Ara h 3-Roasted by BMDCs,and modified Ara h 3 fate in processes involved in immunogenicity and hyper allergenicity,indicating that food processing pattern can change food allergenicity.

麻黄附子细辛汤联合孟鲁司特钠对咳嗽变异性哮喘症状改善及外周血树突状细胞mDCs和pDCs水平的影响

目的分析麻黄附子细辛汤联合孟鲁司特钠对咳嗽变异性哮喘患儿症状改善及外周血髓样树突状细胞(myeloid dendritic cells,mDCs)和浆细胞样树突状细胞(plasmacytoid dendritic cells,pDCs)及肺功能的影响。方法选取医院2019年1月—2020年12月收治的132例咳嗽变异性哮喘患儿作为研究对象。按随机数字表法分为两组,对照组66例,在常规雾化治疗基础上给予孟鲁司特钠治疗;观察组66例,在对照组基础上给予麻黄附子细辛汤治疗。检测两组患儿治疗前、治疗后1、2、3、4周外周血mDCs、pDCs及mDCs/pDCs数据变化、症状改善情况及肺功能的影响。随访1年观察复发情况。结果两组治疗前后外周血mDCs比例没有变化(P>0.05);两组治疗后外周血pDCs比例均持续下降(P<0.05),但观察组治疗后2周和3周外周血pDCs比例低于对照组(P<0.05);两组治疗后mDCs/pDCs比值升高(P<0.05),但观察组治疗后2周和3周的mDCs/pDCs比值高于对照组(P<0.05)。治疗4周后,观察组早晚的咳嗽评分低于对照组(P<0.05);治疗4周后观察组肺功能各指标优于对照组(P<0.05);随访1年后,病例均未脱落,观察组复发率4.55%(3/66)低于对照组15.15%(10/66)(P<0.05)。结论麻黄附子细辛汤联合孟鲁司特钠治疗咳嗽变异性哮喘,更能快速降低外周血pDCs比例、提升mDCs/pDCs比值,有助于快速纠正患儿体内Th1/Th2的失衡状态同时减轻临床症状、优化肺功能,预后较好。

Dendritic cells engineered to secrete anti-Dc R3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro

AIM To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a Cr-51 releasing test. T cell responses induced by RNAloaded DCs were analyzed by measuring cytokine levels, including IFN-gamma, IL-10, IL4, TNF-alpha and IL-12. RESULTS The anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DCtumor- anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated (P < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA (P < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group (P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-gamma and lower level IL4 than those incubated with DC-total tumor RNA or controls (P < 0.01). CONCLUSION DCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network.

Serum IL-10 from systemic lupus erythematosus patients suppresses the differentiation and function of monocyte-derived dendritic cells

The role played by cytokines, other than interferon （IFN）-a, in the differentiation and function of dendritic cells （DCs） in systemic lupus erythematosus （SLE）, remains unclear. Serum interleukin-10 （IL-10） levels are generally elevated in SLE patients, which might modulate the differentiation of DCs. In this study, DCs were induced from monocytes either by transendothelial trafficking or by culture with granulocyte-macrophage colony-stimulating factor （GM-CSF） ＋ IL-4 ＋ tumor necrosis factor （TNF）-a. Both systems were used to investigate the effects of elevated serum IL-10 level on DC differentiation in SLE patients. The results showed that monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the expression of human leukocyte antigen （HLA）-DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited an impaired capacity to stimulate allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved in the pathogenesis of SLE by modulating the differentiation and function of DCs.

The role of plasmacytoid dendritic cells(pDCs)in immunity during viral infections and beyond

Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors.Second,IFNs activate innate and adaptive immunity.Dysregulation of IFN production can lead to severe immune system dysfunction.It is thus crucial to identify and characterize the cellular sources of IFNs,their effects,and their regulation to promote their beneficial effects and limit their detrimental effects,which can depend on the nature of the infected or diseased tissues,as we will discuss.Plasmacytoid dendritic cells(pDCs)can produce large amounts of all IFN subtypes during viral infection.pDCs are resistant to infection by many different viruses,thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses.Therefore,pDCs are considered essential for the control of viral infections and the establishment of protective immunity.A thorough bibliographical survey showed that,in most viral infections,despite being major IFN producers,pDCs are actually dispensable for host resistance,which is achieved by multiple IFN sources depending on the tissue.Moreover,primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs.More surprisingly,pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases.This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.

Immune responses of dendritic cells combined with tumor-derived autophagosome vaccine on hepatocellular carcinoma

Background： To induce and collect tumor-derived autophagosomes （DRibbles） from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. Methods： Dendritic cells （DCs） generated from peripheral blood mononuclear cell （PBMC） of hepatocellular carcinoma （HCC） patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. Results： DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay （ELISA） showed that IFN-γ, levels after vaccination increased than before in most patients, but CDS＋ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ, were detected in the CD8＋ cells than CD4＋ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8＋ T cell responses, supporting it as a tumor vaccine candidate. Conclusions： Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.

Changes of the Transcriptional Levels of Molecules Associated with Endogenous Antigen Processing and Presentation in Porcine Skin-derived Dendritic Cells Infected with PCV2 in vivo

[Objective] This study aimed to investigate the changes of the transcriptional levels of molecules associated with endogenous antigen processing and presenta- tion in porcine skin-derived dendritic cells infected with PCV2 in vivo. [Method] Healthy 40-day-old Landrace piglets were infected with porcine circovirus type 2 （PCV2） and euthanized on the 34, 7rd, 14th, 21st and 35th d post inoculation （DPI）. The porcine skin-derived dendritic cells （DCs） were collected to analyze the transcrip- tional levels of molecules （LMP7, UBP, MHC-I, calreticulin） associated with endogenous antigen processing and presentation by using real-time fluorescent quantitative PCR （real-time FQ-PCR）. [Result] The results showed that the level of LMP7 mR- NAs was reduced significantly on the 3DPI （P〈0.05）; the level of UBP mRNAs was consistently up-regulated, which increased significantly on the 21DPI and 35DPI （P〈 0.05）; the level of MHC-I mRNAs was significantly down-regulated on the 7DPI （P〈 0.05）; the level of calreticulin mRNAs was up-regulated slightly without significant dif- ference. [Conclusion] PCV2 can inhibit the endogenous antigen processing and presentation ability of porcine skin-derived DCs at early stages of infection.

Impact of nanoparticles on immune cells and their potential applications in cancer immunotherapy

Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harvested for numerous bio-medical and biotechnological advancements mainly in cancer treatment.This review article aims to scrutinize various types of nanoparticles that interact differently with immune cells like macrophages,dendritic cells,T lymphocytes,and natural killer(NK)cells.It also underscores the importance of knowing how nanoparticles influence immune cell functions,such as the production of cytokines and the presentation of antigens which are crucial for effective cancer immunotherapy.Hence overviews of bio-molecular mechanisms are provided.Nanoparticles can improve antigen presentation,boost T-cell responses,and overcome the immunosuppressive tumor environment.The regulatory mechanisms,signaling pathways,and nanoparticle characteristics are also presented for a comprehensive understanding.We review the nanotechnology platform options and challenges in nanoparticlesbased immunotherapy,from an immunotherapy perspective including precise targeting,immune modulation,and potential toxicity,as well as personalized approaches based on individual patient and tumor characteristics.The development of emerging multifunctional nanoparticles and theranostic nanoparticles will provide new solutions for the precision and efficiency of cancer therapies in next-generation practice.