An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation

Kae Won Cho, David L. Morris, Jennifer L. delProposto, Lynn Geletka, Brian Zamarron, Gabriel Martinez-Santibanez, Kevin A. Meyer, Kanakadurga Singer, Robert W. O'Rourke, Carey N. Lumeng

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)605-617
Number of pages13
JournalCell Reports
Volume9
Issue number2
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Cho, K. W., Morris, D. L., delProposto, J. L., Geletka, L., Zamarron, B., Martinez-Santibanez, G., Meyer, K. A., Singer, K., O'Rourke, R. W., & Lumeng, C. N. (2014). An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation. Cell Reports, 9(2), 605-617. https://doi.org/10.1016/j.celrep.2014.09.004