Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity
| Autor: | Donal B. O’Connor, Desmond Winters, Mark A. Exley, Ali Tavakkoli, Donal O'Shea, Danielle Duquette, Andrew E. Hogan, Suzanne Stutte, David Alvarez, Selma Boulenouar, Lydia Lynch, Xavier Michelet, Michael B. Brenner, Ulrich H. von Andrian, Christina Dold |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cytotoxicity Immunologic Male medicine.medical_specialty Adoptive cell transfer Adipose tissue macrophages Immunology Adipose tissue Biology 03 medical and health sciences Mice 0302 clinical medicine Immune system Internal medicine medicine Immunology and Allergy Cytotoxic T cell Animals Homeostasis Humans Lymphocytes Obesity skin and connective tissue diseases Macrophage homeostasis Macrophages Innate lymphoid cell Immunity Innate Cell biology body regions Mice Inbred C57BL 030104 developmental biology Infectious Diseases Endocrinology Adipose Tissue 030220 oncology & carcinogenesis Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2017.01.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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