Boulenouar, Selma and Michelet, Xavier and Duquette, Danielle and Alvarez, Daniel and Hogan, Andrew E. and Dold, Christina and O’Connor, Donal and Stutte, Suzanne and Tavakkoli, Ali and Winters, Desmond and Exley, Mark A. and O'Shea, Donal and Brenner, Michael B. and von Andrian, Ulrich and Lynch, Lydia (2017) Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity. Immunity, 46 (2). pp. 273-286. ISSN 1097-4180

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Abstract

Adipose tissue has a dynamic immune system that adapts to changes in diet and maintains homeostatic tissue remodeling. Adipose type 1 innate lymphoid cells (AT1-ILCs) promote pro-inflammatory macrophages in obesity, but little is known about their functions at steady state. Here we found that human and murine adipose tissue harbor heterogeneous populations of AT1-ILCs. Experiments using parabiotic mice fed a high-fat diet (HFD) showed differential trafficking of AT1-ILCs, particularly in response to short- and long-term HFD and diet restriction. At steady state, AT1-ILCs displayed cytotoxic activity toward adipose tissue macrophages (ATMs). Depletion of AT1-ILCs and perforin deficiency resulted in alterations in the ratio of inflammatory to anti-inflammatory ATMs, and adoptive transfer of AT1-ILCs exacerbated metabolic disorder. Diet-induced obesity impaired AT1-ILC killing ability. Our findings reveal a role for AT1-ILCs in regulating ATM homeostasis through cytotoxicity and suggest that this function is relevant in both homeostasis and metabolic disease.

Item Type:	Article
Keywords:	adipose tissue; NK cells; macrophages; metabolism; obesity; cytotoxicity; BET; Natural-Killer-Cells; Obesity; Liver; Inavriant NKT Cells; Tissue Macrophages; Diversity; Differentation; Immunology; Promote; T-Cells; Obesity - immunology; Humans; Mice, Inbred C57BL; Adipose Tissue - cytology; Homeostasis - immunology; Male; Adipose Tissue - immunology; Immunity; Innate; Obesity - pathology; Animals; Lymphocytes - immunology; Female; Mice; Cytotoxicity; Immunologic - immunology; Macrophages - immunology; Animal experimentation; Homeostasis; Medical colleges; Macrophages; Physiological aspects;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	11564
Identification Number:	https://doi.org/10.1016/j.immuni.2017.01.008
Depositing User:	Andrew Hogan
Date Deposited:	01 Nov 2019 16:43
Journal or Publication Title:	Immunity
Publisher:	Elsevier
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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