Brown Adipose Tissue Harbors a Distinct Sub-Population of Regulatory T Cells

Medříková, Daša; Sijmonsma, Tjeerd P.; Sowodniok, Katharina; Richards, David M.; Delacher, Michael; Sticht, Carsten; Gretz, Norbert; Schafmeier, Tobias; Feuerer, Markus; Herzig, Stephan

doi:10.1371/journal.pone.0118534

Cited by 65 publications

(71 citation statements)

References 33 publications

(39 reference statements)

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“…In addition, we showed none of these immune cells change with aging, yet during obesity, B cells increase and macrophages and eosinophils decrease in BAT. Other groups have also shown the presence of macrophages [29][30][31], eosinophils [31,32], T cells [31], regulatory T cells [33], natural killer T (NKT) cells [31], and gamma delta T (γδ T) by guest, on www.jlr.org Downloaded from cells in BAT [31]. In the most thorough study of BAT macrophages, Wolf et al…”

Section: Role Of Adipose Tissue In Systemic Energy Homeostasismentioning

confidence: 99%

Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

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A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts continue seeking interventions to mitigate obesity-associated AT inflammation, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g. beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology. prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7]. Thus, a better understanding of adipose tissue (AT), the organ that expands the most in size during obesity, should provide solutions to this health concern.When discussing AT, white adipose tissue (WAT) is most commonly considered; however, other types of AT, brown adipose tissue (BAT) and beige AT also exist.Adipocytes in WAT and BAT are generated from unique progenitors. WAT stores excess energy in the form of triglycerides. BAT can store small amounts of triglycerides; however, its primary role is to burn fatty acids to generate heat. Beige fat has brown-like properties but is transiently present in WAT depots (especially subcutaneous) upon beta-adrenergic stimulation. Regulation of all three of these fat depots is critically important for lipid and energy homeostasis.WAT consists of spatially distinct beds: visceral, omental, subcutaneous, perivascular, epicardial, and many others. These depots serve to cushion organs they BAT is localized primarily in subscapular regions in rodents, and was only discovered in adult humans in the past decade [10,11]. BAT has a characteristic brown appearance grossly, and is easily distinguished from WAT. This distinctive color is due to the presence of concentrated mitochondria within each brown adipocyte, accompanied by high iron concentrations required for activation of the electron transport chain during beta-oxidation. High expression of uncoupling protein 1 (UCP-1) causes this beta-oxidation to result in generation of heat rather than ATP (thermogenesis), thus assistin...

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Section: Role Of Adipose Tissue In Systemic Energy Homeostasismentioning

confidence: 99%

Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

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“…It was reported that brown adipose tissue from female B6 mice hosts Tregs with a transcriptome different from that of their splenic counterparts and that a small number of transcriptional changes occur upon cold stress in vivo (35). However, comparison of the transcriptomes of Tregs from brown versus visceral white adipose tissue is complicated by the fact that data on the former came from females and the latter from males.…”

Section: Visceral Adipose Tissue Tregs: Regulators Of Organismal Metamentioning

confidence: 99%

“…Ablation of Tregs using a Foxp3-DTR system reduced whole-mouse oxygen consumption and heat generation under 4° cold stress, but not at room temperature (35). This finding suggests that Tregs in brown adipose tissue might regulate the metabolic response to cold stimulation, a notion supported by changes in expression of genes in the thermogenic program at that site.…”

Section: Visceral Adipose Tissue Tregs: Regulators Of Organismal Metamentioning

confidence: 99%

Tissue Tregs

Panduro

Benoist

Mathis

2016

Annu. Rev. Immunol.

454

431

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The immune system is responsible for defending an organism against the myriad of microbial invaders it constantly confronts. It has become increasingly clear that the immune system has a second major function: the maintenance of organismal homeostasis. Foxp3+CD4+ regulatory T cells (Tregs) are important contributors to both of these critical activities, defense being the primary purview of Tregs circulating through lymphoid organs, and homeostasis ensured mainly by their counterparts residing in parenchymal tissues. This review focuses on so-called tissue Tregs. We first survey existing information on the phenotype, function, sustaining factors, and human equivalents of the three best-characterized tissue-Treg populations—those operating in visceral adipose tissue, skeletal muscle, and the colonic lamina propria. We then attempt to distill general principles from this body of work—as concerns the provenance, local adaptation, molecular sustenance, and targets of action of tissue Tregs, in particular.

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“…Although BAT contains a resident population of innate (macrophages and eosinophils) and adaptive (Tregs) immune cells (Medrikova et al, 2015; Nguyen et al, 2011; Tian et al, 2016), their supportive roles in the maintenance of brown fat functions are poorly understood. For example, BAT contains a unique population of Tregs, whose depletion results in macrophage infiltration and BAT inflammation without significantly altering its thermogenic functions (Medrikova et al, 2015). In contrast, two studies have identified PDGFRα + and Sca-1 + stromal cells in adult BAT, which can differentiate into brown adipocytes (Lee et al, 2015b; Schulz et al, 2011).…”

Section: Brown Adipose Tissuementioning

confidence: 99%

Tissue Immunometabolism: Development, Physiology, and Pathobiology

2017

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Evolution of metazoans resulted in the specialization of cellular and tissue function. This was accomplished by division of labor, which allowed tissue parenchymal cells to prioritize their core functions while ancillary functions were delegated to tissue accessory cells, such as immune, stromal, and endothelial cells. In metabolic organs, the accessory cells communicate with their clients, the tissue parenchymal cells, to optimize cellular processes, allowing organisms to adapt to changes in their environment. Here, we discuss tissue immunometabolism from this vantage point, and use examples from adipose tissues (white, beige, and brown) and liver to outline the general principles by which accessory cells support metabolic homeostasis in parenchymal cells. A corollary of this model is that disruption of communication between client and accessory cells might predispose metabolic organs to the development of disease.

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Brown Adipose Tissue Harbors a Distinct Sub-Population of Regulatory T Cells

Cited by 65 publications

References 33 publications

Contributions of innate type 2 inflammation to adipose function

Contributions of innate type 2 inflammation to adipose function

Tissue Tregs

Tissue Immunometabolism: Development, Physiology, and Pathobiology

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