The ron receptor tyrosine kinase regulates macrophage heterogeneity and plays a protective role in diet-induced obesity, atherosclerosis, and hepatosteatosis

Shan Yu, Joselyn N. Allen, Adwitia Dey, Limin Zhang, Gayathri Balandaram, Mary J. Kennett, Mingcan Xia, Na Xiong, Jeffrey Maurice Peters, Andrew David Patterson, Pamela Hankey Giblin

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8 Scopus citations

Abstract

Obesity is a chronic inflammatory disease mediated in large part by the activation of inflammatory macrophages. This chronic inflammation underlies a whole host of diseases including atherosclerosis, hepatic steatosis, insulin resistance, type 2 diabetes, and cancer, among others. Macrophages are generally classified as either inflammatory or alternatively activated. Some tissueresident macrophages are derived from yolk sac erythromyeloid progenitors and fetal liver progenitors that seed tissues during embryogenesis and have the ability to repopulate through local proliferation. These macrophages tend to be anti-inflammatory in nature and are generally involved in tissue remodeling, repair, and homeostasis. Alternatively, during chronic inflammation induced by obesity, bone marrow monocyte-derived macrophages are recruited to inflamed tissues, where they produce proinflammatory cytokines and exacerbate inflammation. The extent to which these two populations of macrophages are plastic in their phenotype remains controversial. We have demonstrated previously that the Ron receptor tyrosine kinase is expressed on tissue-resident macrophages, where it limits inflammatory macrophage activation and promotes a repair phenotype. In this study, we demonstrate that Ron is expressed in a subpopulation of macrophages during chronic inflammation induced by obesity that exhibit a repair phenotype as determined by the expression of arginase 1. In addition, we demonstrate that the Ron receptor plays a protective role in the progression of diet-induced obesity, hepatosteatosis, and atherosclerosis. These results suggest that altering macrophage heterogeneity in vivo could have the potential to alleviate obesity-associated diseases.

Original languageEnglish (US)
Pages (from-to)256-265
Number of pages10
JournalJournal of Immunology
Volume197
Issue number1
DOIs
StatePublished - Jul 1 2016

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All Science Journal Classification (ASJC) codes

  • Immunology

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