Fat‐resident <scp>T</scp>regs: an emerging guard protecting from obesity‐associated metabolic disorders

Chen, X.; Wu, Yuzhang; Wang, L.

doi:10.1111/obr.12033

Cited by 39 publications

(27 citation statements)

References 88 publications

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“…Specifically, regulatory T-cell (Treg) deficiency has been implicated in various autoimmune and metabolic disorders including rheumatoid arthritis, atherosclerosis, diabetes type-1, metabolic syndrome, and multiple sclerosis(30). Patients with GCA and polymyalgia rheumatic (PMR) may have decreased serum levels of these immunosuppressant Treg cells(31).…”

Section: Discussionmentioning

confidence: 99%

Effect of Diabetes Mellitus on Giant Cell Arteritis

Abel

Yashkin

Sloan

et al. 2015

Journal of Neuro-Ophthalmology

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Objective To determine if type 2 diabetes mellitus (DM) is protective against giant cell arteritis (GCA) and to estimate the incidence of GCA diagnosis in the Medicare population. Methods Medicare 5% claims files from 1991-2011 were used to identify beneficiaries diagnosed with DM, but not GCA, within a three-year ascertainment period. Propensity score matching was used to define a control group of non-diabetics with comparable demographic covariates. Competing-risk regression was then used to assess the impact of DM diagnosis on GCA diagnosis. To allow for a three-year ascertainment period, the analysis sample was limited to beneficiaries over 68 years old at baseline. Results A total of 151,041 beneficiaries diagnosed with DM were matched to an equal number of controls. Mean study follow-up was 67.75 months. GCA was diagnosed among 1,116 beneficiaries with DM (0.73%) versus 465 (0.30%) controls. The risk of receiving a GCA diagnosis among patients with DM was increased by 100% (sub hazard ratio (SHR): 2.00; 95% confidence interval (CI): 1.78 2.25). The annual incidence of GCA diagnosis among U.S. Medicare beneficiaries over 68 was 93 in 100,000. Conclusion A DM diagnosis is not protective against a GCA diagnosis in the Medicare population. Our data suggests that a DM diagnosis increases the risk of GCA diagnosis within 5.7 years for Medicare beneficiaries over 68.

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Section: Discussionmentioning

confidence: 99%

Effect of Diabetes Mellitus on Giant Cell Arteritis

Abel

Yashkin

Sloan

et al. 2015

Journal of Neuro-Ophthalmology

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“…The Th17/Treg balance has also been linked with the development of obesity-associated diseases such as type 2 diabetes (T2D) [Table 2; (1, 4, 5, 7, 55–57)]. Immunologically, obesity is characterized by low-grade chronic inflammation with abnormal cytokine production and the activation of various inflammatory pathways, associated with adverse clinical outcomes including insulin resistance and T2D (58).…”

Section: Th17/treg Balance In Metabolic Diseasesmentioning

confidence: 99%

The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System

et al. 2017

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Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of inflammatory diseases that not only affect the gastrointestinal tract but also have whole-body manifestations, including insulin resistance. Epigenetic mechanisms are amenable to both environmental and circulating factors and contribute to determining the T cell landscape. The recently identified participation of the gut microbiota in the remodeling of the epigenome of immune cells has triggered a paradigm shift in our understanding of the etiology of various inflammatory diseases and opened new paths toward therapeutic strategies. In this review, we provide an overview of the contribution of the Th17/Treg balance in the development and progression of inflammatory bowel diseases and metabolic diseases. We discuss the involvement of epigenetic mechanisms in the regulation of T cell function in the particular context of dysbiosis. Finally, we examine the potential for nutritional interventions affecting the gut microbiota to reshape the T cell epigenome and address the inflammatory component of various diseases.

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“…Therefore, maintaining and/or increasing adipose regulatory cells ( e.g. Tregs and/or MDSCs) is crucial for preserving the insulin sensitive status [33], [36], [37].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Metabolic Effects of Rapamycin Are Associated with Enhanced Regulatory Cells in Diet-Induced Obese Mice

et al. 2014

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The “mechanistic target of rapamycin” (mTOR) is a central controller of growth, proliferation and/or motility of various cell-types ranging from adipocytes to immune cells, thereby linking metabolism and immunity. mTOR signaling is overactivated in obesity, promoting inflammation and insulin resistance. Therefore, great interest exists in the development of mTOR inhibitors as therapeutic drugs for obesity or diabetes. However, despite a plethora of studies characterizing the metabolic consequences of mTOR inhibition in rodent models, its impact on immune changes associated with the obese condition has never been questioned so far. To address this, we used a mouse model of high-fat diet (HFD)-fed mice with and without pharmacologic mTOR inhibition by rapamycin. Rapamycin was weekly administrated to HFD-fed C57BL/6 mice for 22 weeks. Metabolic effects were determined by glucose and insulin tolerance tests and by indirect calorimetry measures of energy expenditure. Inflammatory response and immune cell populations were characterized in blood, adipose tissue and liver. In parallel, the activities of both mTOR complexes (e. g. mTORC1 and mTORC2) were determined in adipose tissue, muscle and liver. We show that rapamycin-treated mice are leaner, have enhanced energy expenditure and are protected against insulin resistance. These beneficial metabolic effects of rapamycin were associated to significant changes of the inflammatory profiles of both adipose tissue and liver. Importantly, immune cells with regulatory functions such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were increased in adipose tissue. These rapamycin-triggered metabolic and immune effects resulted from mTORC1 inhibition whilst mTORC2 activity was intact. Taken together, our results reinforce the notion that controlling immune regulatory cells in metabolic tissues is crucial to maintain a proper metabolic status and, more generally, comfort the need to search for novel pharmacological inhibitors of the mTOR signaling pathway to prevent and/or treat metabolic diseases.

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Fat‐resident Tregs: an emerging guard protecting from obesity‐associated metabolic disorders

Cited by 39 publications

References 88 publications

Effect of Diabetes Mellitus on Giant Cell Arteritis

Effect of Diabetes Mellitus on Giant Cell Arteritis

The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System

Beneficial Metabolic Effects of Rapamycin Are Associated with Enhanced Regulatory Cells in Diet-Induced Obese Mice

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