CXCR3 Controls T-Cell Accumulation in Fat Inflammation
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Citações na Scopus
28
Tipo de produção
article
Data de publicação
2014
Título da Revista
ISSN da Revista
Título do Volume
Editora
LIPPINCOTT WILLIAMS & WILKINS
Autores
FOLCO, Eduardo J.
OZDEMIR, Cafer
SHEIKINE, Yuri
CHRISTEN, Thomas
SUKHOVA, Galina K.
TANG, Eva H. C.
LUSTER, Andrew D.
Citação
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, v.34, n.7, p.1374-+, 2014
Resumo
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.
Palavras-chave
adipose tissue, CXCR3, receptors, inflammation, lymphocytes, macrophages, obesity
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