CXCR3 Controls T-Cell Accumulation in Fat Inflammation

Abstract
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 receptor 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.
- Received May 5, 2012.
- Accepted April 17, 2014.
- © 2014 American Heart Association, Inc.
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- CXCR3 Controls T-Cell Accumulation in Fat InflammationViviane Zorzanelli Rocha, Eduardo J. Folco, Cafer Ozdemir, Yuri Sheikine, Thomas Christen, Galina K. Sukhova, Eva H.C. Tang, Marcio Sommer Bittencourt, Raul D. Santos, Andrew D. Luster, David E. Cohen and Peter LibbyArteriosclerosis, Thrombosis, and Vascular Biology. 2014;ATVBAHA.113.303133, originally published May 8, 2014https://doi.org/10.1161/ATVBAHA.113.303133
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- CXCR3 Controls T-Cell Accumulation in Fat InflammationViviane Zorzanelli Rocha, Eduardo J. Folco, Cafer Ozdemir, Yuri Sheikine, Thomas Christen, Galina K. Sukhova, Eva H.C. Tang, Marcio Sommer Bittencourt, Raul D. Santos, Andrew D. Luster, David E. Cohen and Peter LibbyArteriosclerosis, Thrombosis, and Vascular Biology. 2014;ATVBAHA.113.303133, originally published May 8, 2014https://doi.org/10.1161/ATVBAHA.113.303133