Tissular Tregs: A unique population of adipose-tissue-resident Foxp3+CD4+ T cells that impacts organismal metabolism

Cipolletta, Daniela; Kolodin, Dmitriy; Benoist, Christophe; Mathis, Diane

doi:10.1016/j.smim.2011.06.002

Cited by 113 publications

(120 citation statements)

References 94 publications

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“…S7B). Of note, along with the known reduction in VAT-associated Tregs during DIO (4,9,12,27), CD4 + Foxp3 + Treg percentages were increased in the VAT of Stat3 −/− mice compared with Stat3 +/+ mice on a HFD (Fig. 3F).…”

Section: Stat3 In T Cellsmentioning

confidence: 71%

“…At the cellular level, recent studies implicate T cells, B cells, and macrophages in promoting adipose tissue inflammation and regulating high-fat diet (HFD)-induced obesity and insulin resistance (4)(5)(6). Seminal studies have demonstrated that both CD4 + and CD8 + T-cell subsets in obese adipose tissue produce proinflammatory cytokines such as IFN-γ, which drives local inflammation and inhibits insulin signaling (7)(8)(9)(10).…”

mentioning

confidence: 99%

“…B and T cells also can regulate CD11b + F4/80 + adipose tissue M1 and M2 macrophage phenotypes, which exacerbate adipose tissue inflammation (7,9,11). Foxp3 + regulatory T cell (Treg) populations in adipose tissue are inversely correlated with obesity (4,9,12), suggesting that a defect in immune tolerance also promotes obesity, inflammation, and insulin resistance. The key signaling mediators that regulate T-cell-promoted HFD-induced obesity and insulin resistance are largely unexplored, however.…”

mentioning

confidence: 99%

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Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Priceman¹,

Kujawski²,

Shen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

107

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Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown, however. Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3 activity is elevated in obese VAT and in VAT-resident T cells. Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. In addition, Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important mediator and direct target for regulating adipose tissue inflammation, DIO, and its associated metabolic dysfunctions.

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Section: Stat3 In T Cellsmentioning

confidence: 71%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Priceman¹,

Kujawski²,

Shen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

107

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show abstract

“…Treg cells have performed functions such as to suppress inflammatory responses in mucosal interfaces that are constantly exposed to allergens [23], commensal gut microbiota [24,25], transplanted organs [26], pathogenic infections [24], and tumors [27]. Recent studies have suggested a role for Tregs in other situations, such as adipose tissue resident Tregs controlling metabolic disorders [28,29] and Tregs limiting organ rejection [30]. In certain cases, the suppressive function of Tregs limits beneficial effector responses of the host against tumors and chronic infections [31,32].…”

Section: Treg Functionsmentioning

confidence: 99%

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

Torres¹,

López-Casado²,

León³

et al. 2017

Physiology and Pathology of Immunology

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The immune system is responsible for the defense of the organism. It controls what is introduced into it and identifies it as self from non-self. The defensive mechanisms activated by the immune system are directed against pathological microbes and toxic or allergenic proteins, and it must avoid responses that produce excessive damage of self-tissues, inducing tolerance to avoid autoimmunity and other immunopathologies. Regulatory Tcells play an essential role in these active processes, using several distinct suppressive mechanisms. The immune dysregulatory diseases result from defects affecting regulatory T cell development and/or function, including the impact of essential genes mutations for Tregulatory cell functions and the associated autoimmune syndromes.

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“…In support of a similar protective role for Th2 cells, transfer of wild-type but not STAT6 2/2 CD4 + T cells, which have impaired Th2 differentiation, into Rag1 2/2 mice on a HFD normalizes obesity-associated pathologies (10). Although the loss of Th2 cell-derived cytokines likely affects the state of AT macrophage polarization, note that T cell transfer into immunodeficient mice can also induce colitis, and consequent effects on weight, microbiome, and immune homeostasis may confound interpretation of effects on the AT (31). Another subset of regulatory immune cells that is normally found in AT is the invariant NKT (iNKT) cell.…”

Section: Immune Regulation Is Lost In Obese Atmentioning

confidence: 99%

Immune Regulation in Obesity-Associated Adipose Inflammation

Han

Levings

2013

The Journal of Immunology

134

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Adipose tissue inflammation is often a consequence of obesity and is characterized by infiltration and activation of immune cells that overproduce cytokines and chemokines. This apparent loss of immune regulation in obese adipose tissue contributes to the ongoing chronic inflammation that is thought to promote the degradation of metabolic parameters in obesity. Much recent work has sought to identify the immune cell subsets that are involved in adipose tissue inflammation, understand the mechanisms by which adipose tissue inflammation develops, and develop immunotherapeutic strategies to reverse this process. In this review, we describe the known mechanisms that underlie the loss of immune regulation in obesity-associated adipose tissue inflammation and set the stage for the development of novel therapeutic approaches.

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Tissular Tregs: A unique population of adipose-tissue-resident Foxp3+CD4+ T cells that impacts organismal metabolism

Cited by 113 publications

References 94 publications

Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

Immune Regulation in Obesity-Associated Adipose Inflammation

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