Journal article
The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells
A Vasanthakumar, K Moro, A Xin, Y Liao, R Gloury, S Kawamoto, S Fagarasan, LA Mielke, S Afshar-Sterle, SL Masters, S Nakae, H Saito, JM Wentworth, P Li, W Liao, WJ Leonard, GK Smyth, W Shi, SL Nutt, S Koyasu Show all
Nature Immunology | Published : 2015
DOI: 10.1038/ni.3085
Abstract
Foxp3+ regulatory T (Treg) cells in visceral adipose tissue (VAT-Treg cells) are functionally specialized tissue-resident cells that prevent obesity-associated inflammation and preserve insulin sensitivity and glucose tolerance. Their development depends on the transcription factor PPAR-γ; however, the environmental cues required for their differentiation are unknown. Here we show that interleukin 33 (IL-33) signaling through the IL-33 receptor ST2 and myeloid differentiation factor MyD88 is essential for development and maintenance of VAT-Treg cells and sustains their transcriptional signature. Furthermore, the transcriptional regulators BATF and IRF4 were necessary for VAT-Treg differentia..
View full abstractGrants
Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
We thank P. O'Brien for assistance with tissue collection, S. Wada for animal care, M. Febbraio and A. Lew for critical advice, E. Cretney for mice and E. Bandala-Sanchez, V. Bryant and J. Brady for reagents. We are grateful to K. Nakanishi (Hyogo College of Medicine), T. Mak (The Campbell Family Institute for Breast Cancer Research), and U. Klein (Columbia University) for mice. Supported by the National Health and Medical Research Council of Australia (A.K., S.L.N. and G.K.S.), the Sylvia and Charles Viertel Foundation (A.K.), the Australian Research Council (A.K. and S.L.N.), the Diabetes Australia Research Trust (J. M. W.), PRESTO from the Japan Science and Technology Agency (K.M.), and a Grant-in Aid for Scientific Research (B) (26293110 to K.M.) and a Grant-in-Aid for Scientific Research (S) (22229004 to S. Koyasu) from the Japan Society for the Promotion of Science. W.L., P.L. and W.J.L. are supported by the Division of Intramural Research, National Heart, Blood, and Lung Institute, US National Institutes of Health. This study was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme.