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Wuhan, China

Tang T.-T.,Institute of Cardiology | Song Y.,Huazhong University of Science and Technology | Ding Y.-J.,Institute of Cardiology | Liao Y.-H.,Institute of Cardiology | And 10 more authors.
Journal of Lipid Research

regulatory T cells (T reg ) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T reg numbers, suppressive function, serum infl ammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T reg were determined in vitro. Our data revealed that the suppressive function of T reg from RA patients signifi cantly decreased compared with that of control subjects. AT signifi cantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T reg numbers and suppressive functions were signifi cantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T reg from primary T cells and enhanced preexisting T reg function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T reg by AT. In conclusion, AT signifi cantly increased T reg numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled infl ammation in this disorder. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc. Source

Tang T.-T.,Huazhong University of Science and Technology | Yuan J.,Huazhong University of Science and Technology | Zhu Z.-F.,Huazhong University of Science and Technology | Zhang W.-C.,Huazhong University of Science and Technology | And 12 more authors.
Basic Research in Cardiology

Persistent inflammatory responses participate in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We hypothesized that regulatory T (Treg) cells modulate inflammatory responses, attenuate ventricular remodeling and subsequently improve cardiac function after MI. Acute MI was induced by ligation of the left anterior descending coronary artery in rats. Infiltration of Foxp3+ Treg cells was detected in the infarcted heart. Expansion of Treg cells in vivo by means of adoptive transfer as well as a CD28 superagonistic antibody (JJ316) resulted in an increased number of Foxp3+ Treg cells in the infarcted heart. Subsequently, rats with MI showed improved cardiac function following Treg cells transfer or JJ316 injection. Interstitial fibrosis, myocardial matrix metalloproteinase-2 activity and cardiac apoptosis were attenuated in the rats that received Treg cells transfer. Infiltration of neutrophils, macrophages and lymphocytes as well as expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were also significantly decreased, and the CD8+ cardiac-specific cytotoxic T lymphocyte response was inhibited. Expression of interleukin (IL)-10 in the heart, however, was increased. Additional studies in vitro indicated that Treg cells directly protect neonatal rat cardiomyocytes against LPS-induced apoptosis, and this protection depends on the cell-cell contact and IL-10 expression. Furthermore, Treg cells inhibited proinflammatory cytokines production by cardiomyocytes. These data demonstrate that Treg cells serve to protect against adverse ventricular remodeling and contribute to improve cardiac function after myocardial infarction via inhibition of inflammation and direct protection of cardiomyocytes. © 2011 Springer-Verlag. Source

Tang T.-T.,Huazhong University of Science and Technology | Ding Y.-J.,Huazhong University of Science and Technology | Liao Y.-H.,Huazhong University of Science and Technology | Yu X.,Huazhong University of Science and Technology | And 8 more authors.
Cellular Physiology and Biochemistry

Aims: Increasing evidences confirm the role of immune activation in the pathogenesis of chronic heart failure (CHF). Regulatory T cells appear central to the control of immune homeostasis. We assessed the hypothesis that the circulating frequency and function of CD4+CD25+ Foxp3 +CD127low T regulatory cells (Tregs) would be deranged in patients with CHF. Methods: Ninety-nine CHF patients due to non-ischemic (NIHF) or ischemic etiology (IHF) and 24 control donors were enrolled in the study. Frequency of circulating Tregs was evaluated by flow cytometry. Foxp3 in peripheral blood mononuclear cells (PBMCs) was assayed at the mRNA level by real-time PCR. Functional properties of Tregs to suppress proliferation and pro-inflammatory cytokines secretion of activated CD4+CD25 - T cells were measured by proliferation assay and ELISA. Results: The results demonstrated that CHF patients had significantly lower frequency of circulating Tregs and reduced Foxp3 expression in PBMCs compared with control donors. Moreover, Tregs from CHF patients showed compromised function to suppress CD4+CD25- T cells proliferation and pro-inflammatory cytokines secretion. A similar pattern with reduced Tregs frequency and compromised function was found in both NIHF and IHF patients. Correlation analysis suggested that Tregs frequency and function positively correlated with LVEF, whereas negatively correlated with LVEDD and NT-proBNP in patients with CHF. Conclusions: Our data are the first to demonstrate that frequencies of circulating Tregs in patients with CHF are reduced and their suppressive function compromised independently of the etiology. Defective Tregs may be an underlying mechanism of immune activation in CHF patients. Copyright © 2010 S. Karger AG, Basel. Source

Zhang W.-C.,Huazhong University of Science and Technology | Zhang W.-C.,Key Laboratory of Biological Targeted Therapy | Wang J.,Huazhong University of Science and Technology | Wang J.,Key Laboratory of Biological Targeted Therapy | And 27 more authors.
Journal of Biological Chemistry

Regulatory T (Treg) cells play a protective role against the development of atherosclerosis. Previous studies have revealed Treg cell defects in patients with non-ST elevation acute coronary syndrome (NSTACS), but the mechanisms underlying these defects remain unclear. In this study, we found that the numbers of peripheral blood CD4+CD25+CD127low Treg cells and CD4+CD25+CD127lowCD45RA +CD45RO- naive Treg cells were lower in the NSTACS patients than in the chronic stable angina (CSA) and the chest pain syndrome (CPS) patients. However, the number of CD4+CD25+CD127 lowCD45RA- CD45RO+ memory Treg cells was comparable in all of the groups. The frequency of CD4+CD25 +CD127lowCD45RO- CD45RA+CD31 + recent thymic emigrant Treg cells and the T cell receptor excision circle content of purified Treg cells were lower in the NSTACS patients than in the CSA patients and the CPS controls. The spontaneous apoptosis of Treg cells (defined as CD4+CD25+CD127low annexin V +7-AAD-) was increased in the NSTACS patients compared with the CSA and CPS groups. Furthermore, oxidized LDL could induce Treg cell apoptosis, and the oxidized LDL levels were significantly higher in the NSTACS patients than in the CSA and CPS groups. In accordance with the altered Treg cell levels, the concentration of TNF-α was increased in the NSTACS patients, resulting in a decreased IL-10/TNF-α ratio. These findings indicate that the impaired thymic output of Treg cells and their enhanced susceptibility to apoptosis in the periphery were responsible for Treg cell defects observed in the NSTACS patients. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Source

Xu L.,NO1 Hospital of Wuhan | Dong B.,NO1 Hospital of Wuhan | Wang H.,NO1 Hospital of Wuhan | Zeng Z.,NO1 Hospital of Wuhan | And 6 more authors.
Microbes and Infection

In most female patients, the symptoms of genital infection due to Neisseria gonorrhoeae tend to be slight or even absent. Our previous studies suggested that progesterone might play a role in female asymptomatic gonococcal infection. In this study, we demonstrated that progesterone induced the expression of thymic stromal lymphopoietin (TSLP) and regulatory T cells (Treg)-related transcription factor Foxp3, and inhibited the expression of Th17 related transcription factor RORγt, and reduced the influx of neutrophils in murine vaginal gonococcal infection. Blockade of TSLP with antibody partially reversed the effects of progesterone on the murine model of gonococcal vaginal infection. In invitro experiments, progesterone induced a rapid up-regulation of TSLP in vaginal epithelial cells stimulated with N. gonorrhoeae. Blocking thymic stromal lymphopoietin receptor (TSLPR) with a TSLPR monoclonal antibody partially prevented progesterone suppression of IL-17-producing T cells differentiation, and progesterone promotion of CD4+CD25+Foxp3+ regulatory T cells differentiation. Altogether, our results indicate that the progesterone suppresses Th17 cell responses, and enhances the development of Treg cells, through TSLP-dependent mechanisms, and play a role in female asymptomatic gonococcal infections. © 2013 Institut Pasteur. Source

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