CXCR3 controls T-cell accumulation in fat inflammation

Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1374-81. doi: 10.1161/ATVBAHA.113.303133. Epub 2014 May 8.


Objective: Obesity associates with increased numbers of inflammatory cells in adipose tissue (AT), including T cells, but the mechanism of T-cell recruitment remains unknown. This study tested the hypothesis that the chemokine (C-X-C motif) receptor 3 (CXCR3) participates in T-cell accumulation in AT of obese mice and thus in the regulation of local inflammation and systemic metabolism.

Approach and results: Obese wild-type mice exhibited higher mRNA expression of CXCR3 in periepididymal AT-derived stromal vascular cells compared with lean mice. We evaluated the function of CXCR3 in AT inflammation in vivo using CXCR3-deficient and wild-type control mice that consumed a high-fat diet. Periepididymal AT from obese CXCR3-deficient mice contained fewer T cells than obese controls after 8 and 16 weeks on high-fat diet, as assessed by flow cytometry. Obese CXCR3-deficient mice had greater glucose tolerance than obese controls after 8 weeks, but not after 16 weeks. CXCR3-deficient mice fed high-fat diet had reduced mRNA expression of proinflammatory mediators, such as monocyte chemoattractant protein-1 and regulated on activation, normal T cell expressed and secreted, and anti-inflammatory genes, such as Foxp3, IL-10, and arginase-1 in periepididymal AT, compared with obese controls.

Conclusions: These results demonstrate that CXCR3 contributes to T-cell accumulation in periepididymal AT of obese mice. Our results also suggest that CXCR3 regulates the accumulation of distinct subsets of T cells and that the ratio between these functional subsets across time likely modulates local inflammation and systemic metabolism.

Keywords: CXCR3, receptors; adipose tissue; inflammation; lymphocytes; macrophages; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Animals
  • Chemotaxis, Leukocyte*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / genetics
  • Obesity / immunology*
  • Obesity / metabolism
  • Panniculitis / genetics
  • Panniculitis / immunology*
  • Panniculitis / metabolism
  • Receptors, CXCR3 / deficiency
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Time Factors


  • Cxcr3 protein, mouse
  • Inflammation Mediators
  • Receptors, CXCR3