Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin

Jan Mauer; Bhagirath Chaurasia; Julia Goldau; Merly C. Vogt; Johan Ruud; Khoa D. Nguyen; Sebastian Theurich; A. Christine Hausen; Joel Schmitz; Hella S. Broenneke; Emma Estevez; Tamara L. Allen; Andrea Mesaros; Linda Partridge; Mark A. Febbraio; Ajay Chawla; F. Thomas Wunderlich; Jens C. Bruening

doi:10.1038/ni.2865

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Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin

Journal article

Peer reviewed

Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin

Jan Mauer, Bhagirath Chaurasia, Julia Goldau, Merly C. Vogt, Johan Ruud, Khoa D. Nguyen, Sebastian Theurich, A. Christine Hausen, Joel Schmitz, Hella S. Broenneke, …

Nature immunology, Vol.15(5), pp.423-430

05/01/2014

DOI: 10.1038/ni.2865

PMCID: PMC4161471

PMID: 24681566

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Abstract

Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that mice with an inactivated gene encoding the IL-6R. chain of the receptor for IL-6 in myeloid cells (116ra(Delta myel) mice) developed exaggerated deterioration of glucose homeostasis during diet-induced obesity, due to enhanced resistance to insulin. Tissues targeted by insulin showed increased inflammation and a shift in macrophage polarization. IL-6 induced expression of the receptor for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous manner. 116ra(Delta myel) mice were resistant to IL-4-mediated alternative polarization of macrophages and exhibited enhanced susceptibility to lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via IL-6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL-6 in limiting inflammation.

Immunology

Life Sciences & Biomedicine

Science & Technology

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Title: Subtitle: Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin
Creators: Jan Mauer - Max Planck Institute for Metabolism Research
Bhagirath Chaurasia - University of Cologne
Julia Goldau - University of Cologne
Merly C. Vogt - Max Planck Institute for Metabolism Research
Johan Ruud - University of Cologne
Khoa D. Nguyen - University of California, San Francisco
Sebastian Theurich - Max Planck Institute for Metabolism Research
A. Christine Hausen - Max Planck Institute for Metabolism Research
Joel Schmitz - University of Cologne
Hella S. Broenneke - Max Planck Institute for Metabolism Research
Emma Estevez - Baker Heart and Diabetes Institute
Tamara L. Allen - Baker Heart and Diabetes Institute
Andrea Mesaros - Max Planck Institute for Biology of Ageing
Linda Partridge - Max Planck Institute for Biology of Ageing
Mark A. Febbraio - Baker Heart and Diabetes Institute
Ajay Chawla - University of California, San Francisco
F. Thomas Wunderlich - Max Planck Society
Jens C. Bruening - University of Cologne
Resource Type: Journal article
Publication Details: Nature immunology, Vol.15(5), pp.423-430
DOI: 10.1038/ni.2865
PMID: 24681566
PMCID: PMC4161471
NLM abbreviation: Nat Immunol
ISSN: 1529-2908
eISSN: 1529-2916
Publisher: Springer Nature
Number of pages: 11
Grant note: SFB 612; SFB 670 / Deutsche Forschungsgemeinschaft; German Research Foundation (DFG) DP1AR064158 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) DP1AR064158; HL076746; DK094641 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL076746 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) BR 1492/7-1 / Leibniz Preis APP1041760; APP1042465; SPRF APP1021168 / National Health and Medical Research Council of Australia; National Health and Medical Research Council (NHMRC) of Australia R01DK094641 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Language: English
Date published: 05/01/2014
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359875502771

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