Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance

Timothy E. O'Sullivan; Moritz Rapp; Xiying Fan; Orr El Weizman; Priya Bhardwaj; Nicholas M. Adams; Thierry Walzer; Andrew J. Dannenberg; Joseph C. Sun

doi:10.1016/j.immuni.2016.06.016

Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance

Timothy E. O'Sullivan, Moritz Rapp, Xiying Fan, Orr El Weizman, Priya Bhardwaj, Nicholas M. Adams, Thierry Walzer, Andrew J. Dannenberg, Joseph C. Sun

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

163 Scopus citations

Abstract

Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.

Original language	English (US)
Pages (from-to)	428-441
Number of pages	14
Journal	Immunity
Volume	45
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2016.06.016
State	Published - 2016

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

Access to Document

10.1016/j.immuni.2016.06.016

Cite this

Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance. / O'Sullivan, Timothy E.; Rapp, Moritz; Fan, Xiying; Weizman, Orr El; Bhardwaj, Priya; Adams, Nicholas M.; Walzer, Thierry; Dannenberg, Andrew J.; Sun, Joseph C.

In: Immunity, Vol. 45, No. 2, 2016, p. 428-441.

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

@article{33f7ce6471c040aab689cbaff7a10bbe,

title = "Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance",

abstract = "Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.",

author = "O'Sullivan, {Timothy E.} and Moritz Rapp and Xiying Fan and Weizman, {Orr El} and Priya Bhardwaj and Adams, {Nicholas M.} and Thierry Walzer and Dannenberg, {Andrew J.} and Sun, {Joseph C.}",

note = "Funding Information: We thank members of the Sun lab for comments, discussions, technical support, and experimental assistance. We thank Lewis Lanier and Alexander Rudensky for helpful discussions. T.E.O. was supported by the American Cancer Society. M.R. was supported by a fellowship from the DAAD (Germany). X.F. and N.M.A. were supported by the NIH Medical Scientist Training Program grant T32GM07739 to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program. A.J.D. was supported by grants from the NIH (1R01CA154481-01A1), the Breast Cancer Research Foundation, and the Botwinick-Wolfensohn Foundation. J.C.S. was supported by the Ludwig Center for Cancer Immunotherapy, the Searle Scholars Program, the Cancer Research Institute, the Starr Cancer Consortium, and grants from the NIH (AI100874 and P30CA008748). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

year = "2016",

doi = "10.1016/j.immuni.2016.06.016",

language = "English (US)",

volume = "45",

pages = "428--441",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance

AU - O'Sullivan, Timothy E.

AU - Rapp, Moritz

AU - Fan, Xiying

AU - Weizman, Orr El

AU - Bhardwaj, Priya

AU - Adams, Nicholas M.

AU - Walzer, Thierry

AU - Dannenberg, Andrew J.

AU - Sun, Joseph C.

N1 - Funding Information: We thank members of the Sun lab for comments, discussions, technical support, and experimental assistance. We thank Lewis Lanier and Alexander Rudensky for helpful discussions. T.E.O. was supported by the American Cancer Society. M.R. was supported by a fellowship from the DAAD (Germany). X.F. and N.M.A. were supported by the NIH Medical Scientist Training Program grant T32GM07739 to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program. A.J.D. was supported by grants from the NIH (1R01CA154481-01A1), the Breast Cancer Research Foundation, and the Botwinick-Wolfensohn Foundation. J.C.S. was supported by the Ludwig Center for Cancer Immunotherapy, the Searle Scholars Program, the Cancer Research Institute, the Starr Cancer Consortium, and grants from the NIH (AI100874 and P30CA008748). Publisher Copyright: © 2016 Elsevier Inc. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2016

Y1 - 2016

N2 - Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.

AB - Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.

UR - http://www.scopus.com/inward/record.url?scp=84997701962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84997701962&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2016.06.016

DO - 10.1016/j.immuni.2016.06.016

M3 - Article

C2 - 27496734

AN - SCOPUS:84997701962

VL - 45

SP - 428

EP - 441

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -

Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this