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Cell Rep. 2014 Oct 23;9(2):605-17. doi: 10.1016/j.celrep.2014.09.004. Epub 2014 Oct 9.

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

Author information

1
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan-si, Chungcheongnam-do 330-930, South Korea.
2
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
3
Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
4
Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
5
Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Surgery, Ann Arbor Veteran's Administration Hospital, Ann Arbor, MI 48109, USA.
6
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. Electronic address: clumeng@umich.edu.

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.

PMID:
25310975
PMCID:
PMC4252867
DOI:
10.1016/j.celrep.2014.09.004
[Indexed for MEDLINE]
Free PMC Article

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