An MHC II-Dependent Activation Loop between Adipose Tissue Macrophages and CD4+ T Cells Controls Obesity-Induced Inflammation

An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4+ T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs) and CD4+ T cells contribute to adipose tissue metainflammation. Intravital microsc...

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Bibliographic Details
Published in:	Cell reports (Cambridge) 2014-10, Vol.9 (2), p.605-617
Main Authors:	Cho, Kae Won, Morris, David L., DelProposto, Jennifer L., Geletka, Lynn, Zamarron, Brian, Martinez-Santibanez, Gabriel, Meyer, Kevin A., Singer, Kanakadurga, O’Rourke, Robert W., Lumeng, Carey N.
Format:	Article
Language:	eng
Subjects:	Adipose Tissue - cytology Adipose Tissue - immunology Animals CD11c Antigen - metabolism CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cells, Cultured Gene Deletion Genes, MHC Class II HLA-DR Antigens - genetics HLA-DR Antigens - metabolism Humans Lymphocyte Activation Macrophages - immunology Macrophages - metabolism Mice Mice, Inbred C57BL Obesity - immunology
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Summary:	An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4+ T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs) and CD4+ T cells contribute to adipose tissue metainflammation. Intravital microscopy identifies dynamic antigen-dependent interactions between ATMs and T cells in visceral fat. Mice deficient in major histocompatibility complex class II (MHC II) showed protection from diet-induced obesity. Deletion of MHC II expression in macrophages led to an adipose tissue-specific decrease in the effector/memory CD4+ T cells, attenuation of CD11c+ ATM accumulation, and improvement in glucose intolerance by increasing adipose tissue insulin sensitivity. Ablation experiments demonstrated that the maintenance of proliferating conventional T cells is dependent on signals from CD11c+ ATMs in obese mice. These studies demonstrate the importance of MHCII-restricted signals from ATMs that regulate adipose tissue T cell maturation and metainflammation. [Display omitted] •Adipose tissue T cells dynamically interact with ATMs•MHCII in ATMs is required to generate effector/memory T cells with obesity•MHC II in resident ATMs is required for obesity-induced insulin resistance•Ablation of CD11c+ ATMs in obesity attenuates conventional T cell proliferation Obesity triggers an innate and adaptive immune response in adipose tissue, but little is known about how these signals are coordinated. Cho et al. demonstrate the importance of MHC II class-restricted signals from adipose tissue macrophages in controlling obesity-induced T cell activation and the development of insulin resistance. Loss of MHC II from resident tissue macrophages is sufficient to prevent the generation of active effector/memory T cells identifying a target for intervention in metainflammation.
ISSN:	2211-1247 2211-1247