The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications

Zeng, Chun; Shi, Xiaonan; Zhang, Baojun; He, Liu; Zhang, Lianjun; Ding, Wenjun; Zhao, Yong

doi:10.1007/s00109-011-0816-5

Cited by 217 publications

(189 citation statements)

References 42 publications

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“…Our idea was supported by Th1/Th2 ratios calculated as IL-2/IL-4, IL-2/IL-10, IFN-γ/IL-4, IFN-γ/ IL-10 which demonstrated a down-regulation of Th1 and up-regulation of Th2 profile in T2D patients. In fact, the Th2 profile exhibited by insulin-treated T2D patients is consistent with the anti-inflammatory profile of these patients [43][44][45] .…”

Section: Discussionsupporting

confidence: 79%

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Nekoua¹,

Fachinan²,

Atchamou³

et al. 2016

Afr H. Sci.

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Background: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. Objectives:We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). Methods: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed. Results: T2DP were hyperglycemic and showed high level of insulin, normal levels of triglycerides and total-cholesterol and without any change in HDL-cholesterol.Compared to healthy subjects, T2DP exhibited significant decreased frequencies of neutrophils, without any change in monocytes, eosinophils and natural killer cells. The percentages of total lymphocytes (CD3+) and CD8+-T-cells decreased whereas those of regulatory T-cells increased without any change in CD4+ T-cells in T2DP. Interestingly, the frequencies of effector CD4+-T and B-cells increased in T2DP. Serum concentrations of IL-2, IFN-γ and IL-4 decreased while IL-10 significantly enhanced in T2DP, suggesting a differentiation of CD4+T helper cells towards IL-10-producing-Teff-cells in these patients. Conclusion: Insulin-treated type 2 diabetes is associated with anti-inflammatory profile consistent with differentiation of CD4+-Th-cells towards IL-10-producing-Teff-cells, concomitant with increased frequencies of Treg and B-cells, and this may probably offer prevention against certain infections or autoimmune/inflammatory diseases.

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Section: Discussionsupporting

confidence: 79%

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Nekoua¹,

Fachinan²,

Atchamou³

et al. 2016

Afr H. Sci.

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“…As comparable to human studies, several animal experiments indicate that obesity promotes Th17 expansion and subsequent IL-17 production, exacerbating disease severity in murine models of multiple sclerosis and inflammatory bowel disease, both of which are representative Th17-related diseases as well as psoriasis 56 . Furthermore, it has been reported that IL-17A production from PBMCs are increased in type 2 diabetes patients compared with healthy controls 57 , and percentage of haemoglobin A1c, a common clinical marker of diabetes severity, is positively correlated with IL-17 production 54 . Thus, IL-17 is now increasingly recognized as a new mediator of adipose tissue metabolism and inflammation, indicating that psoriasis and obesity-related metabolic disorders have a common immunopathological basis in disease development.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

et al. 2015

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Accumulating epidemiologic evidence has revealed that metabolic syndrome is an independent risk factor for psoriasis development and is associated with more severe psoriasis. Adiponectin, primarily recognized as a metabolic mediator of insulin sensitivity, has been newly drawing attention as a mediator of immune responses. Here we demonstrate that adiponectin regulates skin inflammation, especially IL-17-related psoriasiform dermatitis. Mice with adiponectin deficiency show severe psoriasiform skin inflammation with enhanced infiltration of IL-17-producing dermal Vg4 þ gd-T cells. Adiponectin directly acts on murine dermal gd-T cells to suppress IL-17 synthesis via AdipoR1. We furthermore demonstrate here that the adiponectin level of skin tissue as well as subcutaneous fat is decreased in psoriasis patients. IL-17 production from human CD4-or CD8-positive T cells is also suppressed by adiponectin. Our data provide a regulatory role of adiponectin in skin inflammation, which would imply a mechanism underlying the relationship between psoriasis and metabolic disorders.

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“…5,6 Therefore, CNI agents are now believed to be necessary for prevention of allograft rejection but preferably with reduced doses. 7 Indeed, the imbalance of Th17/Treg has been shown to be associated with the development of inflammatory disorders [8][9][10] and allograft rejection. 11 Treg cells contribute to the induction and maintenance of tolerance of recipients to allografts, 12 while Th17 cells are important to mediate chronic allograft rejection.…”

Section: Introductionmentioning

confidence: 99%

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

et al. 2012

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Suberoylanilide hydroxamic acid (SAHA), as a histone deacetylase (HDAC) inhibitor (HDACi), was recently found to exhibit an immunosuppressive effect. However, whether SAHA can synergize with calcineurin inhibitors (CNIs) to inhibit allograft rejection and its underlying mechanism remain elusive. In this study, we demonstrated the synergistic effects of SAHA and non-therapeutic dose of tacrolimus (FK506) in prolonging the allograft survival in a murine cardiac transplant model. Concomitant intragraft examination revealed that allografts from SAHA-treated recipients showed significantly lower levels of IL-17 expression, and no discernable difference for IL-17 expressions was detected between SAHA-and SAHA/FK506-treated allograft as compared with allografts from FK506-treated animals. In contrast, administration of FK506 significantly suppressed interferon (IFN)-c but increased IL-10 expression as compared with that of SAHA-treated animals, and this effect was independent of SAHA. Interestingly, SAHA synergizes with FK506 to promote Foxp3 and CTLA4 expression. In vitro, SAHA reduced the proportion of Th17 cells in isolated CD4 1 T-cell population and decreased expressions of IL-17A, IL-17F, STAT3 and RORct in these cells. Moreover, SAHA enhances suppressive function of regulatory T (Treg) cells by upregulating the expression of CTLA-4 without affecting T effector cell proliferation, and increased the proportion of Treg by selectively promoting apoptosis of T effector cells. Therefore, SAHA, a HDACi, may be a promising immunosuppressive agent with potential benefit in conjunction with CNI drugs.

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The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications

Cited by 217 publications

References 42 publications

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

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