| First Author | Chung SH | Year | 2010 |
| Journal | Arthritis Res Ther | Volume | 12 |
| Issue | 5 | Pages | R188 |
| PubMed ID | 20939892 | Mgi Jnum | J:164872 |
| Mgi Id | MGI:4835578 | Doi | 10.1186/ar3158 |
| Citation | Chung SH, et al. (2010) CXC chemokine receptor 4 expressed in T cells plays an important role in the development of collagen-induced arthritis. Arthritis Res Ther 12(5):R188 |
| abstractText | ABSTRACT: INTRODUCTION: Chemokines and their receptors are potential therapeutic targets in rheumatoid arthritis (RA). Among these, several studies suggested the involvement of CXC chemokine 4 (CXCR4) and its ligand CXC ligand 12 (SDF-1) in RA pathogenesis. However, the role of these molecules in T cell function is not known completely due to embryonic lethality of Cxcr4 and Sdf-1 deficient mice. In this report, we generated T cell-specific CXCR4 deficient mice and showed that the CXCR4 in T cells is important for the development of collagen-induced arthritis (CIA). METHODS: T cell specific CXCR4 deficient mice were generated using Cre-loxP system. Mice harboring loxP sites flanking exon 2 of Cxcr4 gene (Cxcr4flox/flox) were generated by homologous recombination, and crossed with Cre transgenic mice expressing Cre recombinase under the control of Lck promoter (Cxcr4+/+/Lck-Cre mice) to generate T cell specific Cxcr4-deficient mice (Cxcr4flox/flox/Lck-Cre mice). CIA was induced by immunization with chicken type II collagen and Complete Freund's Adjuvant (CFA). RESULTS: The incidence, but not the severity, of CIA was significantly reduced in Cxcr4flox/flox/Lck-Cre mice compared to Cxcr4+/+/Lck-Cre mice. We found that the expression of CXCR4 was enhanced in activated T cells and the migration of CXCR4-deficient T cells toward SDF-1 was severely impaired. However, antibody production, cellular proliferative response and cytokine production upon treatment with type II collagen (IIC) were normal in these knockout mice, suggesting CXCR4 is not involved in T helper functions. Interestingly, the proportion of CXCR4-expressing T cells was much increased in affected joints compared with that in draining lymph nodes in CIA induced mice, and distribution of Cxcr4flox/flox/Lck-Cre mouse-derived T cells into affected joints were suppressed compared with Cxcr4+/+/Lck-Cre T cells. CONCLUSIONS: These results indicate that CXCR4 expression in T cells is important for the development of CIA by recruiting activated T cells toward inflammatory sites, and suggest that CXCR4 is a good target for the treatment of RA in humans. |
