Citation

The integrin 91 is a key receptor involved in the development of autoimmune diseases. However, the detailed mechanism for the association of 91 integrin with its ligands remains unclear. In this study, we introduce XCL1/lymphotactin, a member of the chemokine family, as a novel ligand for 9 integrin. Using 9 integrin-overexpressing NIH3T3 cells and endogenously 9 integrin-expressing human rhabdomyosarcoma cells, the interaction between XCL1 and 9 integrin was confirmed by pull-down assays. XCL1 enhanced 9 integrin-dependent cell migration of these cells, thus acting on 9 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 9 integrin is involved in these autoimmune disease models. In CAIA, recombinant XCL1 aggravated the disease and this exacerbation was inhibited by an anti-9 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 9 integrin has an important role for autoimmune diseases.