| First Author | Matsumoto N | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 1 | Pages | 82-90 |
| PubMed ID | 28550205 | Mgi Jnum | J:250652 |
| Mgi Id | MGI:6099777 | Doi | 10.4049/jimmunol.1601329 |
| Citation | Matsumoto N, et al. (2017) A Novel alpha9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases. J Immunol 199(1):82-90 |
| abstractText | The integrin alpha9beta1 is a key receptor involved in the development of autoimmune diseases. However, the detailed mechanism for the association of alpha9beta1 integrin with its ligands remains unclear. In this study, we introduce XCL1/lymphotactin, a member of the chemokine family, as a novel ligand for alpha9 integrin. Using alpha9 integrin-overexpressing NIH3T3 cells and endogenously alpha9 integrin-expressing human rhabdomyosarcoma cells, the interaction between XCL1 and alpha9 integrin was confirmed by pull-down assays. XCL1 enhanced alpha9 integrin-dependent cell migration of these cells, thus acting on alpha9 integrin as a chemoattractant. We also analyzed the in vivo function of XCL1 in the development of anti-type II collagen Ab-induced inflammatory arthritis (CAIA) in BALB/c mice and experimental autoimmune encephalomyelitis in C57BL/6 mice, because alpha9 integrin is involved in these autoimmune disease models. In CAIA, recombinant XCL1 aggravated the disease and this exacerbation was inhibited by an anti-alpha9 integrin Ab. An XCL1-neutralizing Ab produced in this study also ameliorated CAIA. Furthermore, the XCL1-neutralizing Ab abrogated the disease progression in experimental autoimmune encephalomyelitis. Therefore, to our knowledge this study provides the first in vitro and in vivo evidence that the interaction between XCL1 and alpha9 integrin has an important role for autoimmune diseases. |
