BAFF antagonist attenuates the development of skin fibrosis in Tight-Skin Mice
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Abstract
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-γ-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-γ, 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. © 2007 The Society for Investigative Dermatology.
Journal
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- Journal of Investigative Dermatology
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Journal of Investigative Dermatology 127 (12), 2772-2780, 2007-12-01
The Society for Investigative Dermatology / Nature Publishing Group
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Details 詳細情報について
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- CRID
- 1050001335983912960
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- NII Article ID
- 120005756483
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- NII Book ID
- AA00700733
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- ISSN
- 0022202X
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- Web Site
- http://hdl.handle.net/2297/45184
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles