CXCR3 controls T-cell accumulation in fat inflammation.
Arterioscler Thromb Vasc Biol
; 34(7): 1374-81, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24812325
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. APPROACH ANDRESULTS:
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
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paniculite
/
Quimiotaxia de Leucócito
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Tecido Adiposo
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Subpopulações de Linfócitos T
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Receptores CXCR3
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Obesidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Ano de publicação:
2014
Tipo de documento:
Article