Adipose tissue dendritic cell signals are required to maintain T cell homeostasis and obesity-induced expansion

Mol Cell Endocrinol. 2020 Apr 5;505:110740. doi: 10.1016/j.mce.2020.110740. Epub 2020 Jan 24.

Abstract

Adipose tissue derived chronic inflammation is a critical component of obesity induced type II diabetes. Major histocompatibility complex II (MHCII) mediated T cell activation within adipose tissue is one mechanism that contributes to this phenotype. However, the contribution of dendritic cells as professional antigen presenting cells in adipose issue has not previously been explored. Using ItgaxCre x MHCIIfl/fl (M11cKO) mice we observed adipose tissue specific changes in adipose tissue leukocytes. While there was a complete knockout of MHCII in dendritic cells, MHCII was also absent on the majority of macrophages. This resulted in reduction of TCR expression in CD4+ T cells in obese adipose tissue, and an increase in CD8+ and CD4+ CD8+ double positive T cells with decreased CD4+ T cells independent of diet type. Increased CD8+ cells were not observed in the spleen, suggesting adipose tissue T cell regulation is tissue specific. In vitro studies demonstrated more potent antigen presentation function in adipose tissue dendritic cells compared to macrophages. Obese M11cKO mice had decreased CD11c+ adipose tissue macrophages. Despite the changes of immune cellularity in adipose tissue, M11cKO largely did not change inflammatory gene expression in adipose tissue and did not demonstrate differences in glucose and insulin intolerance. Overall MHCII expression on CD11c+ cells is important for maintaining CD4+ and CD8+ adipose tissue T cells, but these cellular changes fail to alter inflammatory output and systemic metabolism.

Keywords: Adipose tissue T cells; Adipose tissue dendritic cells; White adipose tissue.

Publication types

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

MeSH terms

  • Adipose Tissue / pathology*
  • Animals
  • Antigen Presentation / immunology
  • CD11 Antigens / metabolism
  • Cell Proliferation
  • Dendritic Cells / pathology*
  • Gene Expression Regulation
  • Glucose / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Homeostasis*
  • Inflammation / genetics
  • Inflammation / pathology
  • Insulin Resistance
  • Macrophages / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / immunology*
  • Phenotype
  • Signal Transduction*
  • Spleen / pathology
  • T-Lymphocytes / immunology*

Substances

  • CD11 Antigens
  • Histocompatibility Antigens Class II
  • Glucose