CXCR3 Controls T-Cell Accumulation in Fat Inflammation

Carregando...
Imagem de Miniatura
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
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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
Referências
  1. Appay V, 2001, TRENDS IMMUNOL, V22, P83, DOI 10.1016/S1471-4906(00)01812-3
  2. Bronte V, 2003, TRENDS IMMUNOL, V24, P302, DOI 10.1016/S1471-4906(03)00132-7
  3. Feuerer M, 2009, NAT MED, V15, P930, DOI 10.1038/nm.2002
  4. Gordon S, 2003, NAT REV IMMUNOL, V3, P23, DOI 10.1038/nri978
  5. Gregor MF, 2011, ANNU REV IMMUNOL, V29, P415, DOI 10.1146/annurev-immunol-031210-101322
  6. Hancock WW, 2000, J EXP MED, V192, P1515, DOI 10.1084/jem.192.10.1515
  7. Heller EA, 2006, CIRCULATION, V113, P2301, DOI 10.1161/CIRCULATIONAHA.105.605121
  8. Kanda H, 2006, J CLIN INVEST, V116, P1494, DOI 10.1172/JC126498
  9. Kang HW, 2013, J BIOL CHEM, V288, P33376, DOI 10.1074/jbc.M113.481408
  10. Keophiphath M, 2010, ARTERIOSCL THROM VAS, V30, P39, DOI 10.1161/ATVBAHA.109.197442
  11. Kintscher U, 2008, ARTERIOSCL THROM VAS, V28, P1304, DOI 10.1161/ATVBAHA.108.165100
  12. Lim S, 2013, INT J CARDIOL, V169, P166, DOI 10.1016/j.ijcard.2013.08.077
  13. Liu LP, 2005, CURR TOP DEV BIOL, V68, P149, DOI 10.1016/S0070-2153(05)68006-4
  14. Long SA, 2011, J IMMUNOL, V187, P2061, DOI 10.4049/jimmunol.1003224
  15. Lumeng CN, 2007, J CLIN INVEST, V117, P175, DOI 10.1172/JCI29881
  16. Mach F, 1999, J CLIN INVEST, V104, P1041, DOI 10.1172/JCI6993
  17. Nishimura S, 2009, NAT MED, V15, P914, DOI 10.1038/nm.1964
  18. NISHINA PM, 1993, LIPIDS, V28, P599, DOI 10.1007/BF02536053
  19. Okamoto Y, 2008, CIRC RES, V102, P218, DOI 10.1161/CIRCRESAHA.107.164988
  20. PAIGEN B, 1987, ATHEROSCLEROSIS, V64, P215, DOI 10.1016/0021-9150(87)90249-8
  21. Pfaffl MW, 2002, NUCLEIC ACIDS RES, V30, DOI 10.1093/nar/30.9.e36
  22. Platt N, 1996, P NATL ACAD SCI USA, V93, P12456, DOI 10.1073/pnas.93.22.12456
  23. Rocha VZ, 2008, CIRC RES, V103, P467, DOI 10.1161/CIRCRESAHA.108.177105
  24. Rocha VZ, 2011, INT J INFLAM, V2011, DOI 10.4061/2011/529061
  25. Van Wanrooij EJA, 2008, ARTERIOSCL THROM VAS, V28, P251, DOI 10.1161/ATVBAHA.107.147827
  26. Veillard NR, 2005, CIRCULATION, V112, P870, DOI 10.1161/CIRCULATIONAHA.104.520718
  27. Weisberg SP, 2003, J CLIN INVEST, V112, P1796, DOI 10.1172/JCI2000319246
  28. Weisberg SP, 2006, J CLIN INVEST, V116, P115, DOI 10.1172/JCI24335
  29. WHITELAND JL, 1995, J HISTOCHEM CYTOCHEM, V43, P313
  30. Winer S, 2009, NAT MED, V15, P921, DOI 10.1038/nm.2001
  31. Wu HZ, 2007, CIRCULATION, V115, P1029, DOI 10.1161/CIRCULATIONAHA.106.638379
  32. Xu HY, 2003, J CLIN INVEST, V112, P1821, DOI 10.1172/JCI200319451