Cytokine and metabolic regulation of adipose tissue Tregs-Immunometabolism-CSCIED科技核心评价数据库-手机版

Cytokine and metabolic regulation of adipose tissue Tregs

Cytokine and metabolic regulation of adipose tissue Tregs

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DOI	10.1097/IN9.0000000000000013
刊名	Immunometabolism IJ
年，卷(期)	2022, 4(4)
作者	Elkins, Cody; Li, Chaoran,
作者单位	[Elkins, Cody; Li, Chaoran] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA; [Elkins, Cody; Li, Chaoran] Emory Univ, Laney Grad Sch, Immunol & Mol Pathogenesis Grad Program, Grad Div Biol & Biomed Sci, Atlanta, GA 30322 USA
摘要	Since their discovery over a decade ago, much has been learned regarding the importance and function of visceral adipose tissue (VAT)-resident regulatory T cells (Tregs). VAT Tregs play a critical role in controlling VAT inflammation and alleviating metabolic disease. However, this population is disrupted in obesity which exacerbates VAT inflammation and metabolic abnormalities. Therefore, understanding the factors governing the accumulation and maintenance of VAT Tregs, both at steady state and under disease conditions, is crucial for identifying the mechanisms underlying obesity-associated metabolic disease and developing novel therapies. Expansion and maintenance of the VAT Treg compartment is strongly influenced by factors in the local tissue microenvironment, including cytokines, T-cell receptor ligands, hormones, and various metabolites. This mini-review will primarily focus on recent advances in our understandings regarding the regulation of mouse epididymal VAT (eVAT) Tregs, which are the most thoroughly characterized VAT Treg population, by tissue microenvironmental factors and cellular metabolic processes. We will also briefly discuss the limited knowledge available regarding the regulation of mouse ovarian VAT (oVAT) Tregs and human omental VAT Tregs, highlight some lingering questions, and provide a prospective view on where the field is heading.
Abstract	Since their discovery over a decade ago, much has been learned regarding the importance and function of visceral adipose tissue (VAT)-resident regulatory T cells (Tregs). VAT Tregs play a critical role in controlling VAT inflammation and alleviating metabolic disease. However, this population is disrupted in obesity which exacerbates VAT inflammation and metabolic abnormalities. Therefore, understanding the factors governing the accumulation and maintenance of VAT Tregs, both at steady state and under disease conditions, is crucial for identifying the mechanisms underlying obesity-associated metabolic disease and developing novel therapies. Expansion and maintenance of the VAT Treg compartment is strongly influenced by factors in the local tissue microenvironment, including cytokines, T-cell receptor ligands, hormones, and various metabolites. This mini-review will primarily focus on recent advances in our understandings regarding the regulation of mouse epididymal VAT (eVAT) Tregs, which are the most thoroughly characterized VAT Treg population, by tissue microenvironmental factors and cellular metabolic processes. We will also briefly discuss the limited knowledge available regarding the regulation of mouse ovarian VAT (oVAT) Tregs and human omental VAT Tregs, highlight some lingering questions, and provide a prospective view on where the field is heading.
关键词	VAT Treg; obesity; metabolism; inflammation; cytokine
KeyWord	VAT Treg; obesity; metabolism; inflammation; cytokine
基金项目
页码	1-7

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[1]. Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775–87. doi: 10.1016/j.cell.2008.05.009.

[2]. Whibley N, Tucci A, Powrie F. Regulatory T cell adaptation in the intestine and skin. Nat Immunol. 2019;20(4):386–96. doi: 10.1038/s41590-019-0351-z.

[3]. Munoz-Rojas AR, Mathis D. Tissue regulatory T cells: regulatory chameleons. Nat Rev Immunol. 2021;21(9):597–611. doi: 10.1038/s41577-021-00519-w.

[4]. Panduro M, Benoist C, Mathis D. Tissue tregs. Annu Rev Immunol. 2016;34:609–33. doi: 10.1146/annurev-immunol-032712-095948.

[5]. Li C, Spallanzani RG, Mathis D. Visceral adipose tissue Tregs and the cells that nurture them. Immunol Rev. 2020;295(1):114–25. doi: 10.1111/imr.12850.

[6]. Deiuliis J, Shah Z, Shah N, et al. Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers. PLoS One. 2011;6(1):e16376. doi: 10.1371/journal.pone.0016376.

[7]. Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930–9. doi: 10.1038/nm.2002.

[8]. Cipolletta D, Cohen P, Spiegelman BM, et al. Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARgamma effects. Proc Natl Acad Sci USA. 2015;112(2):482–7. doi: 10.1073/pnas.1423486112.

[9]. Li C, Wang G, Sivasami P, et al. Interferon-alpha producing plasmacytoid dendritic cells drive the loss of adipose tissue regulatory T cells during obesity. Cell Metab. 2021;33(8):1610–23.e5. doi: 10.1016/j.cmet.2021.06.007.

[10]. Eller K, Kirsch A, Wolf AM, et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes. 2011;60(11):2954–62. doi: 10.2337/db11-0358.

[11]. Cipolletta D, Feuerer M, Li A, et al. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature. 2012;486(7404):549–53. doi: 10.1038/nature11132.

[12]. Vasanthakumar A, Moro K, Xin A, et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue resident regulatory T cells. Nat Immunol. 2015;16(3):276–85. doi: 10.1038/ni.3085.

[13]. Bapat SP, Myoung Suh J, Fang S, et al. Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature. 2015;528(7580):137–41. doi: 10.1038/nature16151.

[14]. Kolodin D, van Panhuys N, Li C, et al. Antigen and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice. Cell Metab. 2015;21(4):543–57. doi: 10.1016/j.cmet.2015.03.005.

[15]. Li C, DiSpirito JR, Zemmour D, et al. TCR transgenic mice reveal stepwise, multi-site acquisition of the distinctive fat-Treg phenotype. Cell. 2018;174(2):285–99.e12. doi: 10.1016/j.cell.2018.05.004.

[16]. Li C, Munoz-Rojas AR, Wang G, et al. PPAR gamma marks splenic precursors of multiple nonlymphoid-tissue Treg compartments. Proc Natl Acad Sci USA. 2021;118(13):e2025197118. doi: 10.1073/pnas.2025197118.

[17]. Li Y, Lu Y, Lin SH, et al. Insulin signaling establishes a developmental trajectory of adipose regulatory T cells. Nat Immunol. 2021;22(9):1175–85. doi: 10.1038/s41590-021-01010-3.

[18]. Delacher M, Imbusch CD, Hotz-Wagenblatt A, et al. Precursors for nonlymphoid-tissue Treg cells reside in secondary lymphoid organs and are programmed by the transcription factor BATF. Immunity. 2020;52(2):295–312.e11. doi: 10.1016/j.immuni.2019.12.002.

[19]. Vasanthakumar A, Chisanga D, Blume J, et al. Sex specific adipose tissue imprinting of regulatory T cells. Nature. 2020;579(7800):581–85. doi: 10.1038/s41586-020-2040-3.

[20]. Han JM, Wu D, Denroche HC, et al. IL-33 reverses an obesity- induced deficit in visceral adipose tissue ST2+ T regulatory cells and ameliorates adipose tissue inflammation and insulin resistance. J Immunol. 2015;194(10):4777–83. doi: 10.4049/jimmunol.1500020.

[21]. Molofsky AB, Van Gool F, Liang HE, et al. Interleukin-33 and interferon-gamma counter-regulate group 2 innate lymphoid cell activation during immune perturbation. Immunity. 2015;43(1):161–74. doi: 10.1016/j.immuni.2015.05.019.

[22]. Hemmers S, Schizas M, Rudensky AY. Treg cell-intrinsic requirements for ST2 signaling in health and neuroinflammation. J Exp Med. 2021;218(2):e20201234. doi: 10.1084/jem.20201234.

[23]. Zhao XY, Zhou L, Chen Z, et al. The obesity-induced adipokine sST2 exacerbates adipose Treg and ILC2 depletion and promotes insulin resistance. Sci Adv. 2020;6(20):eaay6191. doi: 10.1126/sciadv.aay6191.

[24]. Bradley D, Smith AJ, Blaszczak A, et al. Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity. Nat Commun. 2022;13(1):5606. doi: 10.1038/s41467-022-33067-5.

[25]. Fernandes RA, Li C, Wang G, et al. Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo. Elife. 2020;9:e58463. doi: 10.7554/eLife.58463.

[26]. Molofsky AB, Savage AK, Locksley RM. Interleukin-33 in tissue homeostasis, injury, and inflammation. Immunity. 2015;42(6):1005–19. doi: 10.1016/j.immuni.2015.06.006.

[27]. Spallanzani RG, Zemmour D, Xiao T, et al. Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors. Sci Immunol. 2019;4(35):eaaw3658. doi: 10.1126/sciimmunol.aaw3658.

[28]. Mahlakoiv T, Flamar AL, Johnston LK, et al. Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33. Sci Immunol. 2019;4(35):eaax0416. doi: 10.1126/sciimmunol.aax0416.

[29]. Malko D, Elmzzahi T, Beyer M. Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology. Front Immunol. 2022;13:954798. doi: 10.3389/fimmu.2022.954798.

[30]. Deng T, Liu J, Deng YR, et al. Adipocyte adaptive immunity mediates diet-induced adipose inflammation and insulin resistance by decreasing adipose Treg cells. Nat Commun. 2017;8(1):15725. doi: 10.1038/ncomms15725.

[31]. Wang HY, Lee DA, Peng G, et al. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity. 2004;20(1):107–18. doi: 10.1016/s1074-7613(03)00359-5.

[32]. Stadinski BD, Blevins SJ, Spidale NA, et al. A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3(+) Treg cell development. Nat Immunol. 2019;20(8):1046–58. doi: 10.1038/s41590-019-0414-1.

[33]. Leonard JD, Gilmore DC, Dileepan T, et al. Identification of natural regulatory T cell epitopes reveals convergence on a dominant autoantigen. Immunity. 2017;47(1):107–17.e8. doi: 10.1016/j.immuni.2017.06.015.

[34]. Chang E, Varghese M, Singer K. Gender and sex differences in adipose tissue. Curr Diab Rep. 2018;18(9):69. doi: 10.1007/s11892-018-1031-3.

[35]. Pettersson US, Walden TB, Carlsson PO, et al. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One. 2012;7(9):e46057. doi: 10.1371/journal.pone.0046057.

[36]. Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells. Nat Immunol. 2016;17(6):618–25. doi: 10.1038/ni.3466.

[37]. Voss K, Hong HS, Bader JE, et al. A guide to interrogating immunometabolism. Nat Rev Immunol. 2021;21(10):637–52. doi: 10.1038/s41577-021-00529-8.

[38]. Hartmann FJ, Mrdjen D, McCaffrey E, et al. Single-cell metabolic profiling of human cytotoxic T cells. Nat Biotechnol. 2021;39(2):186–97. doi: 10.1038/s41587-020-0651-8.

[39]. Karmaus PWF, Chen X, Lim SA, et al. Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity. Nature. 2019;565(7737):101–5. doi: 10.1038/s41586-018-0806-7.

[40]. Gaublomme JT, Yosef N, Lee Y, et al. Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell. 2015;163(6):1400–12. doi: 10.1016/j.cell.2015.11.009.

[41]. Arguello RJ, Combes AJ, Char R, et al. SCENITH: a flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab. 2020;32(6):1063–75.e7. doi: 10.1016/j.cmet.2020.11.007.

[42]. Koch MA, Thomas KR, Perdue NR, et al. T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor beta2. Immunity. 2012;37(3):501–10. doi: 10.1016/j.immuni.2012.05.031.

[43]. Mittelsteadt KL, Hayes ET, Campbell DJ. ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue. J Exp Med. 2021;218(6):e20201142. doi: 10.1084/jem.20201142.

[44]. Wu D, Han JM, Yu X, et al. Characterization of regulatory T cells in obese omental adipose tissue in humans. Eur J Immunol. 2019;49(2):336–47. doi: 10.1002/eji.201847570.

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Elkins, Cody; Li, Chaoran. Cytokine and metabolic regulation of adipose tissue Tregs [J]. Immunometabolism. 2022; 4; (4). 1 - 7.

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