Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17...Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.展开更多
Objective:To investigate the correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia.Methods:200 children with pneumonia who were treated i...Objective:To investigate the correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia.Methods:200 children with pneumonia who were treated in our hospital between April 2015 and August 2017 were selected as the pneumonia group, and 100 healthy children who were vaccinated in this hospital during the same period were selected as the normal control group. The differences in serum levels of nutrients, Th1/Th2 cytokines, Th17/Treg cytokines and inflammatory mediators were compared between the two groups. Pearson test was used to assess the relationship between serum nutrient levels and disease severity.Results: Serum Vit A, Fe and Zn levels of pneumonia group were lower than those of control group. The differences in serum Vit D, Ca and Mg levels were not statistically significant between the two groups of children. Serum Th1 cytokines IL-2 and TNF-β contents of pneumonia group were lower than those of control group whereas Th2 cytokines IL-4 and IL-5 contents were higher than those of control group;Th17 cytokines IL-17, IL-21 and IL-22 contents were higher than those of control group whereas Treg cytokines IL-10 and TGF-β contents were lower than those of control group;inflammatory mediators CRP, PCT and MCP-1 contents were significantly higher than those of control group. Pearson test showed that serum nutrients Vit A, Fe and Zn levels in children with pneumonia were directly correlated with the degree of immune cell differentiation and inflammatory response.Conclusion: Serum Vit A, Fe, Zn and other nutrient levels abnormally decrease in children with pneumonia, and the specific level are directly correlated with the severity of the disease.展开更多
Objective: To study the correlation between Treg/Th17 imbalance and the liver injury caused by systemic inflammatory response and oxidative stress in children with sepsis. Methods:A total of 43 children who were diagn...Objective: To study the correlation between Treg/Th17 imbalance and the liver injury caused by systemic inflammatory response and oxidative stress in children with sepsis. Methods:A total of 43 children who were diagnosed with sepsis in Shanghai Jiading District Central Hospital between February 2016 and March 2017were selected as the sepsis group of the study, and children who received physical examination in Outpatient Clinic of Shanghai Jiading District Central Hospital during the same period were selected as the control group of the study. The peripheral blood was collected to determine the contents of Treg and Th17 as well as the expression of oxidative stress molecules, and serum was collected to determine the contents of inflammatory reaction molecules, oxidative stress molecules and liver injury indexes. Results: Peripheral blood Treg and Th17 contents as well as Treg/Th17 of sepsis group were significantly higher than those of control group;serum ALT, AST, TBIL, γ-GT, MIF, sTREM-1, sVCAM-1 and PCT contents as well as peripheral blood MPO and Nrf-2 mRNA expression of sepsis group were significantly higher than those of control group and positively correlated with peripheral blood Treg/Th17 while peripheral blood Keap-1 mRNA expression as well as serum SOD and GSH contents was significantly lower than that of control group and negatively correlated with peripheral blood Treg/Th17. Conclusion: The increase of Treg/Th17 in peripheral blood of children with sepsis is closely related to the activation of inflammatory response and oxidative stress response and the injury of liver function.展开更多
Objective: To discuss the correlation of serum YKL-40 content with eosinophil function as well as Th1/Th2 and Treg/Th17 immunity in patients with allergic rhinitis. Methods: A total of 310 patients with allergic rhini...Objective: To discuss the correlation of serum YKL-40 content with eosinophil function as well as Th1/Th2 and Treg/Th17 immunity in patients with allergic rhinitis. Methods: A total of 310 patients with allergic rhinitis who were treated in the hospital between January 2015 and May 2017 were selected as allergic rhinitis group and 100 healthy volunteers who received physical examination in the hospital during the same period were selected as normal control group. The differences in serum YKL-40 content, eosinophil function as well as Th1/Th2 and Treg/Th17 cytokine contents were compared between the two groups. Pearson test was used to assess the correlation between serum YKL-40 content and disease severity in patients with allergic rhinitis. Results: Serum YKL-40 content of allergic rhinitis group was higher than that of normal control group;serum eosinophil function IgE and Eotaxin-2 contents of allergic rhinitis group were higher than those of normal control group;serum Th1 cytokines IFN-γand IL-12 contents were lower than those of normal control group while Th2 cytokines IL-4 and IL-13 contents were higher than those of normal control group;serum Treg cytokine TGF-β content was lower than that of normal control group while Th17 cytokine IL-17 content was higher than that of normal control group. Pearson test showed that serum YKL-40 content in patients with allergic rhinitis was directly correlated with the eosinophil function as well as Th1/Th2 and Treg/Th17 immunity. Conclusion: Serum YKL-40 content is abnormally high in patients with allergic rhinitis, and the specific expression is positively correlated with the disease severity.展开更多
BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical e...BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.展开更多
AIM:To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells,to observe T-cell phenotypes during hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACHBLF)and to anal...AIM:To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells,to observe T-cell phenotypes during hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACHBLF)and to analyze changes in Th17 and Treg phenotypes during disease progression.METHODS:We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18ACHBLF,18 chronic hepatitis B(CHB)disease controls and 10 healthy controls(HCs)by real-time quantitative pCR and enzyme linked immunosorbent assay.peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry.RESULTS:From the onset of ACHBLF,patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels,which were sustained throughout the disease course.The Treg-related cytokine IL-2and Foxp3 were also up-regulated from disease onset,and Foxp3 gene expression showed a gradually increasing trend during ACHBLF.The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF.At disease onset,Th17 frequency increased significantly compared with both CHB and HCs,but Treg cell frequency decreased significantly compared with CHB.During the ACHBLF event,Th17 frequency remained higher compared with HCs,but decreased sharply from the peak point to the recovery point;Treg cell frequency increased gradually during the ACHBLF event.Treg and Th17 cell counts correlated with ACHBLF development;in all patients,serum IL-17 levels significantly correlated with patient serum ALT levels.In survivors,Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient’s model for end stage liver disease(MELD)plus sodium(MELD-Na)score.The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival.Low Treg/Th17 cell ratios at the onset predicted poor survival.Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time,and subsequently displayed a continuous increase.CONCLUSION:Treg and Th17 cells showed changes in genes,protein levels and T cell phenotypes during ACHBLF events.An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients.展开更多
The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key c...The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10,in addition to high expression of the transcription factor FOXP3.On the other hand,there is a predominance of cytokines associated with the Th1 and Th17 responses among H.pylori-positive adults.In the last few years,the participation of the Th17 response in the gastric inflammation against H.pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario,and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection.Moreover,this cytokine profile might play a pivotal role in the effectiveness of anti-H.pylori vaccines.It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H.pylori,and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.展开更多
The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)a...The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.展开更多
结节病是一种原因不明的多系统累及的肉芽肿性疾病,主要侵犯肺和淋巴系统,其次是眼部和皮肤.肉芽肿是最复杂的免疫反应之一,涉及多种细胞,且细胞分子间的相互作用随时间而动态变化.近年对结节病发病机制的新见解不断涌现,包括结节病的...结节病是一种原因不明的多系统累及的肉芽肿性疾病,主要侵犯肺和淋巴系统,其次是眼部和皮肤.肉芽肿是最复杂的免疫反应之一,涉及多种细胞,且细胞分子间的相互作用随时间而动态变化.近年对结节病发病机制的新见解不断涌现,包括结节病的先天免疫、Th17细胞、Treg细胞、血清淀粉样蛋白A(serum amyloid A protein,SAA)和其他因素的作用.展开更多
文摘Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.
文摘Objective:To investigate the correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia.Methods:200 children with pneumonia who were treated in our hospital between April 2015 and August 2017 were selected as the pneumonia group, and 100 healthy children who were vaccinated in this hospital during the same period were selected as the normal control group. The differences in serum levels of nutrients, Th1/Th2 cytokines, Th17/Treg cytokines and inflammatory mediators were compared between the two groups. Pearson test was used to assess the relationship between serum nutrient levels and disease severity.Results: Serum Vit A, Fe and Zn levels of pneumonia group were lower than those of control group. The differences in serum Vit D, Ca and Mg levels were not statistically significant between the two groups of children. Serum Th1 cytokines IL-2 and TNF-β contents of pneumonia group were lower than those of control group whereas Th2 cytokines IL-4 and IL-5 contents were higher than those of control group;Th17 cytokines IL-17, IL-21 and IL-22 contents were higher than those of control group whereas Treg cytokines IL-10 and TGF-β contents were lower than those of control group;inflammatory mediators CRP, PCT and MCP-1 contents were significantly higher than those of control group. Pearson test showed that serum nutrients Vit A, Fe and Zn levels in children with pneumonia were directly correlated with the degree of immune cell differentiation and inflammatory response.Conclusion: Serum Vit A, Fe, Zn and other nutrient levels abnormally decrease in children with pneumonia, and the specific level are directly correlated with the severity of the disease.
文摘Objective: To study the correlation between Treg/Th17 imbalance and the liver injury caused by systemic inflammatory response and oxidative stress in children with sepsis. Methods:A total of 43 children who were diagnosed with sepsis in Shanghai Jiading District Central Hospital between February 2016 and March 2017were selected as the sepsis group of the study, and children who received physical examination in Outpatient Clinic of Shanghai Jiading District Central Hospital during the same period were selected as the control group of the study. The peripheral blood was collected to determine the contents of Treg and Th17 as well as the expression of oxidative stress molecules, and serum was collected to determine the contents of inflammatory reaction molecules, oxidative stress molecules and liver injury indexes. Results: Peripheral blood Treg and Th17 contents as well as Treg/Th17 of sepsis group were significantly higher than those of control group;serum ALT, AST, TBIL, γ-GT, MIF, sTREM-1, sVCAM-1 and PCT contents as well as peripheral blood MPO and Nrf-2 mRNA expression of sepsis group were significantly higher than those of control group and positively correlated with peripheral blood Treg/Th17 while peripheral blood Keap-1 mRNA expression as well as serum SOD and GSH contents was significantly lower than that of control group and negatively correlated with peripheral blood Treg/Th17. Conclusion: The increase of Treg/Th17 in peripheral blood of children with sepsis is closely related to the activation of inflammatory response and oxidative stress response and the injury of liver function.
基金National Natural Science Foundation of China NO:81460094.
文摘Objective: To discuss the correlation of serum YKL-40 content with eosinophil function as well as Th1/Th2 and Treg/Th17 immunity in patients with allergic rhinitis. Methods: A total of 310 patients with allergic rhinitis who were treated in the hospital between January 2015 and May 2017 were selected as allergic rhinitis group and 100 healthy volunteers who received physical examination in the hospital during the same period were selected as normal control group. The differences in serum YKL-40 content, eosinophil function as well as Th1/Th2 and Treg/Th17 cytokine contents were compared between the two groups. Pearson test was used to assess the correlation between serum YKL-40 content and disease severity in patients with allergic rhinitis. Results: Serum YKL-40 content of allergic rhinitis group was higher than that of normal control group;serum eosinophil function IgE and Eotaxin-2 contents of allergic rhinitis group were higher than those of normal control group;serum Th1 cytokines IFN-γand IL-12 contents were lower than those of normal control group while Th2 cytokines IL-4 and IL-13 contents were higher than those of normal control group;serum Treg cytokine TGF-β content was lower than that of normal control group while Th17 cytokine IL-17 content was higher than that of normal control group. Pearson test showed that serum YKL-40 content in patients with allergic rhinitis was directly correlated with the eosinophil function as well as Th1/Th2 and Treg/Th17 immunity. Conclusion: Serum YKL-40 content is abnormally high in patients with allergic rhinitis, and the specific expression is positively correlated with the disease severity.
基金the Wenzhou Basic Medical and Health Science and Technology Project,No.Y20210307.
文摘BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.
基金Supported by Grants from Shanghai Natural Science Fund,No.09ZR1400500National Natural Science Foundation of China No.30972600Shanghai Health Bureau Fund,No.2012092
文摘AIM:To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells,to observe T-cell phenotypes during hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACHBLF)and to analyze changes in Th17 and Treg phenotypes during disease progression.METHODS:We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18ACHBLF,18 chronic hepatitis B(CHB)disease controls and 10 healthy controls(HCs)by real-time quantitative pCR and enzyme linked immunosorbent assay.peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry.RESULTS:From the onset of ACHBLF,patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels,which were sustained throughout the disease course.The Treg-related cytokine IL-2and Foxp3 were also up-regulated from disease onset,and Foxp3 gene expression showed a gradually increasing trend during ACHBLF.The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF.At disease onset,Th17 frequency increased significantly compared with both CHB and HCs,but Treg cell frequency decreased significantly compared with CHB.During the ACHBLF event,Th17 frequency remained higher compared with HCs,but decreased sharply from the peak point to the recovery point;Treg cell frequency increased gradually during the ACHBLF event.Treg and Th17 cell counts correlated with ACHBLF development;in all patients,serum IL-17 levels significantly correlated with patient serum ALT levels.In survivors,Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient’s model for end stage liver disease(MELD)plus sodium(MELD-Na)score.The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival.Low Treg/Th17 cell ratios at the onset predicted poor survival.Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time,and subsequently displayed a continuous increase.CONCLUSION:Treg and Th17 cells showed changes in genes,protein levels and T cell phenotypes during ACHBLF events.An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients.
文摘The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10,in addition to high expression of the transcription factor FOXP3.On the other hand,there is a predominance of cytokines associated with the Th1 and Th17 responses among H.pylori-positive adults.In the last few years,the participation of the Th17 response in the gastric inflammation against H.pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario,and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection.Moreover,this cytokine profile might play a pivotal role in the effectiveness of anti-H.pylori vaccines.It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H.pylori,and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.
基金by the National Natural Science Foundation of China(81571462,81600353,and 81701472)Jiangsu Provincial Key Medical Center(YXZXB2016004)+1 种基金Jiangsu Biobank of Clinical Resources(BM2015004)Jiangsu Province Grant for Science and Technology(BK20161106).
文摘The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.
文摘结节病是一种原因不明的多系统累及的肉芽肿性疾病,主要侵犯肺和淋巴系统,其次是眼部和皮肤.肉芽肿是最复杂的免疫反应之一,涉及多种细胞,且细胞分子间的相互作用随时间而动态变化.近年对结节病发病机制的新见解不断涌现,包括结节病的先天免疫、Th17细胞、Treg细胞、血清淀粉样蛋白A(serum amyloid A protein,SAA)和其他因素的作用.