| First Author | Matsushita Y | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 1 | Pages | 698-707 |
| PubMed ID | 17579093 | Mgi Jnum | J:143152 |
| Mgi Id | MGI:3822983 | Doi | 10.4049/jimmunol.179.1.698 |
| Citation | Matsushita Y, et al. (2007) Intercellular adhesion molecule-1 deficiency attenuates the development of skin fibrosis in tight-skin mice. J Immunol 179(1):698-707 |
| abstractText | The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis, develops cutaneous fibrosis. Although a fibrillin 1 gene mutation and immunological abnormalities have been demonstrated, the roles of adhesion molecules have not been investigated. To directly assess roles of adhesion molecules in skin fibrosis, TSK/+ mice lacking L-selectin and/or ICAM-1 were generated. The deficiency of ICAM-1, but not L-selectin, significantly suppressed ( approximately 48%) the development of skin sclerosis in TSK/+ mice. Similarly, ICAM-1 antisense oligonucleotides inhibited skin fibrosis in TSK/+ mice. Although T cell infiltration was modest into the skin of TSK/+ mice, ICAM-1 deficiency down-regulated this migration, which is consistent with the established roles of endothelial ICAM-1 in leukocyte infiltration. In addition, altered phenotype or function of skin fibroblasts was remarkable and dependent on ICAM-1 expression in TSK/+ mice. ICAM-1 expression was augmented on TSK/+ dermal fibroblasts stimulated with IL-4. Although growth or collagen synthesis of TSK/+ fibroblasts cultured with IL-4 was up-regulated, it was suppressed by the loss or blocking of ICAM-1. Collagen expression was dependent on the strain of fibroblasts, but not on the strain of cocultured T cells. Thus, our findings indicate that ICAM-1 expression contributes to the development of skin fibrosis in TSK/+ mice, especially via ICAM-1 expressed on skin fibroblasts. |
