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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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*

Substances

  • CD11c Antigen
  • HLA-DR Antigens