Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the re...Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was no展开更多
Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important ro...Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.展开更多
AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into ...AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) 展开更多
BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory resp...BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P <0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728). CONCLUSION EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL- 23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.展开更多
IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma...IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.展开更多
Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carci...Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.展开更多
The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,...The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.展开更多
Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver ...Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver injury,inflammatory cells,inflammatory mediators,cytokines,and the gut microbiome.In the current review,we discuss recent data on a large number of cytokines that play important roles in regulating liver injury,inflammation,fibrosis,and regeneration,with a focus on interferons and T helper(Th)1,Th2,Th9,Th17,interleukin(IL)-1 family,IL-6 family,and IL-20 family cytokines.Hepatocytes can also produce certain cytokines(such as IL-7,IL-11;and IL-33),and the functions of these cytokines in the liver are briefly summarized.Several cytokines have great therapeutic potential,and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases,which are also described.展开更多
AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was adminis...AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.展开更多
IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this ...IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this cytokine has been poorly understood. Here, we show that IL-22 is expressed at both mRNA and protein levels by a novel subset of TH cells that also makes IL-17. IL-22 and IL-17 were found to be coordinately regulated by TGFI3 and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis. However, IL-22 does not regulate TH differentiation; exogenous IL-22 or an IL-22 antagonist had no effect on TH differentiation. These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-l 7 signaling pathways in tissue inflammation and autoimmune diseases.展开更多
Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the mi...Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides T helper (Th) 1 and Th2 cell immune responses, other subsets of T cells, namely Th17 and regulatory T cells, are likely associated with disease progression. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.展开更多
Follicular helper T cells （Tfh） have been referred as a lineage that provides a help for B cells to proliferate and undergo antibody affinity maturation in the germinal center. Evidence has supported that Tfh subset...Follicular helper T cells （Tfh） have been referred as a lineage that provides a help for B cells to proliferate and undergo antibody affinity maturation in the germinal center. Evidence has supported that Tfh subset development, like other lineages, is dependent on microenvironment where a particular transcriptional program is initiated. It has been shown that Bcl-6 and IL-21 act as master regulators for the development and function of Tfh cells. Tfh dysregulation is involved in the development of autoimmune pathologies, such as systemic lupus erythematosus, rheumatoid arthritis and other autoimmune diseases. The present review highlights the recent advances in the field of Tfh cells and focus on their development and function.展开更多
AIM To investigate the levels, ratios, and clinical significance of T helper 17(Th17) cells and regulatory T(Treg) cells in the peripheral blood of patients with autoimmune liver disease(AILD). METHODS F o r t y-t w o...AIM To investigate the levels, ratios, and clinical significance of T helper 17(Th17) cells and regulatory T(Treg) cells in the peripheral blood of patients with autoimmune liver disease(AILD). METHODS F o r t y-t w o A I L D p a t i e n t s w e r e i n c l u d e d i n t h e experimental group(group E), and 11 healthy subjects were recruited as the control group(group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients. RESULTS The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C(P < 0.01), whereas the percentage of Tregs was lower in the group E patients(P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission(P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment(P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD.CONCLUSION A high Th17/Treg ratio appears to predict poor shortterm prognosis in patients with AILD in the active stage.展开更多
文摘Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was no
基金Supported by NIH KO8 DK093578CCFA Career Development Award 3467(DQS)F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
文摘Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.
基金Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China),No. 2008ZX10002-007, No. 2012ZX10002-007the Foundation of Shaanxi Provincial Science and Technology Plan Projects,No. 2011K14-09-09
文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL)
基金the National Natural Science Foundation of China,No.81701881the Nanjing Medical Science and Technology Development Foundation,No.YKK15098 and No.YKK17102
文摘BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P <0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728). CONCLUSION EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL- 23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.
文摘IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.
基金Supported by The National Natural Science Foundation of China,No.81070341 and No.81270517
文摘Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.
基金by the Division of Intramural Research of NIAID(US National Institutes of Health).
文摘The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.
基金supported by the intramural program of the NIAAA(Bin Gao),U01 AA022614,and R01 DK099205(Tatiana Kisseleva)and AA011576 and AA017729(Gyongyi Szabo).
文摘Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver injury,inflammatory cells,inflammatory mediators,cytokines,and the gut microbiome.In the current review,we discuss recent data on a large number of cytokines that play important roles in regulating liver injury,inflammation,fibrosis,and regeneration,with a focus on interferons and T helper(Th)1,Th2,Th9,Th17,interleukin(IL)-1 family,IL-6 family,and IL-20 family cytokines.Hepatocytes can also produce certain cytokines(such as IL-7,IL-11;and IL-33),and the functions of these cytokines in the liver are briefly summarized.Several cytokines have great therapeutic potential,and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases,which are also described.
基金Supported by National Natural Science Foundation of China,No.81260083Grants from the Guangxi Natural Science Foundation of China,No.2014jj AA40237
文摘AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.
文摘IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this cytokine has been poorly understood. Here, we show that IL-22 is expressed at both mRNA and protein levels by a novel subset of TH cells that also makes IL-17. IL-22 and IL-17 were found to be coordinately regulated by TGFI3 and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis. However, IL-22 does not regulate TH differentiation; exogenous IL-22 or an IL-22 antagonist had no effect on TH differentiation. These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-l 7 signaling pathways in tissue inflammation and autoimmune diseases.
基金Supported by Grants from the National Natural Science Foundation of China,No.81061120521 and No.81270470Shanghai Science and Technology Commission,No.12XD1404000
文摘Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides T helper (Th) 1 and Th2 cell immune responses, other subsets of T cells, namely Th17 and regulatory T cells, are likely associated with disease progression. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
基金brue de la Ferollerie, Orleans, France ACKNOWLEDGEMENTS This work was supported in part by grants from the National Institutes of Health ROI AR 059103, Arthritis Foundation Wright Foundation the Outstanding Youth Scientist Investigator Award from National Nature Science Foundation of China （30728007） and the American College of Rheumatology Research and Education＇s Within Our Reach： Finding a Cure for Rheumatoid Arthritis campaign （all to SGZ）, National Nature Science Foundation of China （30972951） （XH） and Le Studium and European FEDER grant support （BR）.
文摘Follicular helper T cells （Tfh） have been referred as a lineage that provides a help for B cells to proliferate and undergo antibody affinity maturation in the germinal center. Evidence has supported that Tfh subset development, like other lineages, is dependent on microenvironment where a particular transcriptional program is initiated. It has been shown that Bcl-6 and IL-21 act as master regulators for the development and function of Tfh cells. Tfh dysregulation is involved in the development of autoimmune pathologies, such as systemic lupus erythematosus, rheumatoid arthritis and other autoimmune diseases. The present review highlights the recent advances in the field of Tfh cells and focus on their development and function.
基金Supported by the Tianqing Liver Disease Research Foundation,China Foundation for Hepatitis Prevention and Control,No.TQGB20150026Kejiaoxingwei Project of Suzhou,No.KJXW2016004
文摘AIM To investigate the levels, ratios, and clinical significance of T helper 17(Th17) cells and regulatory T(Treg) cells in the peripheral blood of patients with autoimmune liver disease(AILD). METHODS F o r t y-t w o A I L D p a t i e n t s w e r e i n c l u d e d i n t h e experimental group(group E), and 11 healthy subjects were recruited as the control group(group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients. RESULTS The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C(P < 0.01), whereas the percentage of Tregs was lower in the group E patients(P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission(P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment(P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD.CONCLUSION A high Th17/Treg ratio appears to predict poor shortterm prognosis in patients with AILD in the active stage.
