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Title: Sex-specific adipose tissue imprinting of regulatory T cells.
Austin Authors: Vasanthakumar, Ajithkumar;Chisanga, David;Blume, Jonas;Gloury, Renee;Britt, Kara;Henstridge, Darren C;Zhan, Yifan;Torres, Santiago Valle;Liene, Sebastian;Collins, Nicholas;Cao, Enyuan;Sidwell, Tom;Li, Chaoran;Spallanzani, Raul German;Liao, Yang;Beavis, Paul A;Gebhardt, Thomas;Trevaskis, Natalie;Nutt, Stephen L;Zajac, Jeffrey D ;Davey, Rachel A;Febbraio, Mark A;Mathis, Diane;Shi, Wei;Kallies, Axel
Affiliation: Institute of Experimental Immunology, University of Bonn, Bonn, Germany
Department of Immunology, Harvard Medical School, Boston, MA, USA
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
College of Health and Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
Department of Computing and Information Systems, The University of Melbourne, Melbourne, Victoria, Australia
Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: Mar-2020 2020-02-26
Publication information: Nature 2020; 579(7800): 581-585
Abstract: Adipose tissue is an energy store and a dynamic endocrine organ1,2. In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism3,4. Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes5,6. Regulatory T (Treg) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT7-9. Here we uncover pronounced sexual dimorphism in Treg cells in the VAT. Male VAT was enriched for Treg cells compared with female VAT, and Treg cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. Heightened inflammation in the male VAT facilitated the recruitment of Treg cells via the CCL2-CCR2 axis. Androgen regulated the differentiation of a unique IL-33-producing stromal cell population specific to the male VAT, which paralleled the local expansion of Treg cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident Treg cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in Treg cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.
DOI: 10.1038/s41586-020-2040-3
ORCID: 0000-0001-5121-0209
PubMed URL: 32103173
Type: Journal Article
Appears in Collections:Journal articles

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