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Sex-specific adipose tissue imprinting of regulatory T cells

Citation

Vasanthakumar, A and Chisanga, D and Blume, J and Gloury, R and Britt, K and Henstridge, DC and Zhan, Y and Torres, SV and Liene, S and Collins, N and Cao, E and Sidwell, T and Li, C and Spallanzani, RG and Liao, Y and Beavis, PA and Gebhardt, T and Trevaskis, N and Nutt, SL and Zajac, JD and Davey, RA and Febbraio, MA and Mathis, D and Shi, W and Kallies, A, Sex-specific adipose tissue imprinting of regulatory T cells, Nature, 579, (7800) pp. 581-585. ISSN 0028-0836 (2020) [Refereed Article]

Copyright Statement

Copyright 2020 The Author(s), under exclusive licence to Springer Nature Limited

DOI: doi:10.1038/s41586-020-2040-3

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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:139619
Year Published:2020
Web of Science® Times Cited:41
Deposited By:Health Sciences
Deposited On:2020-06-23
Last Modified:2020-07-23
Downloads:0

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