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CXCR3 controls T-cell accumulation in fat inflammation.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2014 Jul; Vol. 34 (7), pp. 1374-81. Date of Electronic Publication: 2014 May 08. - Publication Year :
- 2014
-
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 (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.<br />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.<br />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.<br /> (© 2014 American Heart Association, Inc.)
- Subjects :
- Adipose Tissue metabolism
Animals
Disease Models, Animal
Gene Expression Regulation
Inflammation Mediators metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity genetics
Obesity metabolism
Panniculitis genetics
Panniculitis metabolism
Receptors, CXCR3 deficiency
Receptors, CXCR3 genetics
Signal Transduction
T-Lymphocyte Subsets metabolism
Time Factors
Adipose Tissue immunology
Chemotaxis, Leukocyte
Obesity immunology
Panniculitis immunology
Receptors, CXCR3 metabolism
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 34
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 24812325
- Full Text :
- https://doi.org/10.1161/ATVBAHA.113.303133