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Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity.

Research paper by Selma S Boulenouar, Xavier X Michelet, Danielle D Duquette, David D Alvarez, Andrew E AE Hogan, Christina C Dold, Donal D O'Connor, Suzanne S Stutte, Ali A Tavakkoli, Desmond D Winters, Mark A MA Exley, Donal D O'Shea, Michael B MB Brenner, Ulrich U von Andrian, Lydia L Lynch

Indexed on: 24 Feb '17Published on: 24 Feb '17Published in: Immunity



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.

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