Sex-specific adipose tissue imprinting of regulatory T cells
Authors: Tom Sidwell
Rachel A Davey
Mark A Febbraio
Chaoran Li
Paul A Beavis
David Chisanga
Axel Kallies
Yang Liao
Santiago Valle Torres
Diane Mathis
Nicholas Collins
Ajithkumar Vasanthakumar
Wei Shi
Yifan Zhan
Stephen L Nutt
Darren C Henstridge
Jonas Blume
Natalie Trevaskis
Sebastian Liene
Thomas Gebhardt
Jeffrey D Zajac
Renee Gloury
Kara Britt
Enyuan Cao
Raul German Spallanzani
Journal: Nature (2020)
Discipline: Multidisciplinary
Keywords: Adipose tissue; Visceral adipose tissue; Regulatory T cells; FOXP3; Sexual dimorphism
Affiliations: 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. ., The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia., Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia., Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., College of Health and Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia., Institute of Experimental Immunology, University of Bonn, Bonn, Germany., Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia., Department of Immunology, Harvard Medical School, Boston, MA, USA., Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia., Department of Computing and Information Systems, The University of Melbourne, Melbourne, Victoria, Australia.

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. 

Retracted: No

PubPeer comments:
 Figure 1u2014figure supplement 4 A of elife paper (Kikani et al., 2016 ; 10.7554 eLife.17985) is very similar to the panel in Fig S4A of this PNAS paper. Could the authors check? ![file] , 
 According to the authors an Erratum was submitted https: pubpeer.com publications E2BEDE377517C77618F7931F39DA35#3 One year after, the wrong panel is still on the article, and no Erratum was published ![file] ,