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

Selma Boulenouar; Xavier Michelet; Danielle Duquette; David Alvarez; Andrew E. Hogan; Christina Dold; Donal O'Connor; Suzanne Stutte; Ali Tavakkoli; Desmond Winters; Mark A. Exley; Donal O'Shea; Michael B. Brenner; Ulrich von Andrian; Lydia Lynch

doi:10.1016/j.immuni.2017.01.008

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

Selma Boulenouar, Xavier Michelet, Danielle Duquette, David Alvarez, Andrew E. Hogan, Christina Dold, Donal O'Connor, Suzanne Stutte, Ali Tavakkoli, Desmond Winters, Mark A. Exley, Donal O'Shea, Michael B. Brenner, Ulrich von Andrian, Lydia Lynch

Research output: Contribution to journal › Article › peer-review

156 Scopus citations

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.

Original language	English (US)
Pages (from-to)	273-286
Number of pages	14
Journal	Immunity
Volume	46
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2017.01.008
State	Published - Feb 21 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

Keywords

NK cells
adipose tissue
cytotoxicity
macrophages
metabolism
obesity

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10.1016/j.immuni.2017.01.008

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Boulenouar, S., Michelet, X., Duquette, D., Alvarez, D., Hogan, A. E., Dold, C., O'Connor, D., Stutte, S., Tavakkoli, A., Winters, D., Exley, M. A., O'Shea, D., Brenner, M. B., von Andrian, U., & Lynch, L. (2017). Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity. Immunity, 46(2), 273-286. https://doi.org/10.1016/j.immuni.2017.01.008

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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.",

keywords = "NK cells, adipose tissue, cytotoxicity, macrophages, metabolism, obesity",

author = "Selma Boulenouar and Xavier Michelet and Danielle Duquette and David Alvarez and Hogan, {Andrew E.} and Christina Dold and Donal O'Connor and Suzanne Stutte and Ali Tavakkoli and Desmond Winters and Exley, {Mark A.} and Donal O'Shea and Brenner, {Michael B.} and {von Andrian}, Ulrich and Lydia Lynch",

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year = "2017",

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doi = "10.1016/j.immuni.2017.01.008",

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Boulenouar, S, Michelet, X, Duquette, D, Alvarez, D, Hogan, AE, Dold, C, O'Connor, D, Stutte, S, Tavakkoli, A, Winters, D, Exley, MA, O'Shea, D, Brenner, MB, von Andrian, U & Lynch, L 2017, 'Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity', Immunity, vol. 46, no. 2, pp. 273-286. https://doi.org/10.1016/j.immuni.2017.01.008

TY - JOUR

T1 - Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity

AU - Boulenouar, Selma

AU - Michelet, Xavier

AU - Duquette, Danielle

AU - Alvarez, David

AU - Hogan, Andrew E.

AU - Dold, Christina

AU - O'Connor, Donal

AU - Stutte, Suzanne

AU - Tavakkoli, Ali

AU - Winters, Desmond

AU - Exley, Mark A.

AU - O'Shea, Donal

AU - Brenner, Michael B.

AU - von Andrian, Ulrich

AU - Lynch, Lydia

PY - 2017/2/21

Y1 - 2017/2/21

N2 - 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.

AB - 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.

KW - NK cells

KW - adipose tissue

KW - cytotoxicity

KW - macrophages

KW - metabolism

KW - obesity

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M3 - Article

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AN - SCOPUS:85013967225

SN - 1074-7613

VL - 46

SP - 273

EP - 286

JO - Immunity

JF - Immunity

IS - 2

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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