title: Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity.
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.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Selma
authors.initials: S
authors.lastname: Boulenouar
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Michelet
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Duquette
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.affiliation: Education Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Hogan
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Christina
authors.initials: C
authors.lastname: Dold
authors.affiliation: Education Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland.
authors.forename: Donal
authors.initials: D
authors.lastname: O'Connor
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Stutte
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Tavakkoli
authors.affiliation: Education Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland.
authors.forename: Desmond
authors.initials: D
authors.lastname: Winters
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Exley
authors.affiliation: Education Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland.
authors.forename: Donal
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Andrian
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. Electronic address: llynch@bwh.harvard.edu.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lynch
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology* / Q000473:pathology
keywords: NK cells; adipose tissue; cytotoxicity; macrophages; metabolism; obesity