| First Author | Heller EA | Year | 2006 |
| Journal | Circulation | Volume | 113 |
| Issue | 19 | Pages | 2301-12 |
| PubMed ID | 16682613 | Mgi Jnum | J:122449 |
| Mgi Id | MGI:3714424 | Doi | 10.1161/CIRCULATIONAHA.105.605121 |
| Citation | Heller EA, et al. (2006) Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation 113(19):2301-12 |
| abstractText | BACKGROUND: Studies to define the overall contribution of lymphocytes to lesion formation in atherosclerosis-susceptible mice have demonstrated relatively subtle effects; the use of lymphocyte-deficient mice, however, compromises both the effector and regulatory arms of the immune system. Here, we tested the hypothesis that deletion of CXCL10 (IP-10), a chemokine specific for effector T cells that has been localized within atherosclerotic lesions, would significantly inhibit atherogenesis. METHODS AND RESULTS: Compound deficient Apoe(-/-)/Cxcl10(-/-) mice fed a Western-style diet for either 6 or 12 weeks demonstrated significant reductions in atherogenesis as compared with Apoe(-/-) controls, as assessed by both aortic en face and cross-sectional analyses. Immunohistochemical studies revealed a decrease in the accumulation of CD4+ T cells, whereas quantitative polymerase chain reaction analysis of lesion-rich aortic arches demonstrated a marked reduction in mRNA for CXCR3, the CXCL10 chemokine receptor. Although overall T-cell accumulation was diminished significantly, we found evidence to suggest that regulatory T-cell (Treg) numbers and activity were enhanced, as assessed by increased message for the Treg-specific marker Foxp3, as well as increases in immunostaining for the Treg-associated cytokines interleukin-10 and transforming growth factor-beta1. We also documented naturally occurring Treg cells in human atherosclerotic lesions. CONCLUSIONS: We provide novel evidence for a functional role for the effector T-cell chemoattractant CXCL10 in atherosclerotic lesion formation by modulating the local balance of the effector and regulatory arms of the immune system. |
