| First Author | Matsushita T | Year | 2007 |
| Journal | J Invest Dermatol | Volume | 127 |
| Issue | 12 | Pages | 2772-80 |
| PubMed ID | 17581616 | Mgi Jnum | J:127329 |
| Mgi Id | MGI:3763578 | Doi | 10.1038/sj.jid.5700919 |
| Citation | Matsushita T, et al. (2007) BAFF antagonist attenuates the development of skin fibrosis in tight-skin mice. J Invest Dermatol 127(12):2772-80 |
| abstractText | The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis (SSc), develops cutaneous fibrosis and autoimmunity. Although immunological abnormalities have been demonstrated in TSK/+ mice, the roles of B-cell-activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, have not been investigated. Serum BAFF levels in TSK/+ mice were examined by ELISA. Newborn TSK/+ mice were treated with BAFF antagonist, and then skin fibrosis of 8-week-old mice was assessed. Serum BAFF levels were significantly elevated in TSK/+ mice. Remarkably, BAFF antagonist inhibited the development of skin fibrosis, hyper-gamma-globulinemia, and the autoantibody production in TSK/+ mice. The skin from TSK/+ mice showed upregulated expressions of fibrogenic cytokines, such as IL-6 and IL-10, while BAFF antagonist significantly suppressed them. Reciprocally, BAFF antagonist augmented antifibrogenic cytokines, such as IFN-gamma, in the skin of TSK/+ mice. Furthermore, TSK/+ B cells with BAFF stimulation had a significantly enhanced ability to produce IL-6. The results suggest that BAFF/BAFF receptor system is critical for the development of skin fibrosis in TSK/+ mice and could be a potent therapeutical target. |
