BAFF antagonist attenuates the development of skin fibrosis in tight-skin mice

J Invest Dermatol. 2007 Dec;127(12):2772-80. doi: 10.1038/sj.jid.5700919. Epub 2007 Jun 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • B-Cell Activating Factor / antagonists & inhibitors*
  • B-Cell Activating Factor / blood
  • B-Cell Activating Factor / genetics*
  • B-Cell Activating Factor / physiology
  • B-Cell Activation Factor Receptor / metabolism*
  • B-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Female
  • Fibrosis / genetics*
  • Fibrosis / pathology
  • Gene Expression Regulation*
  • Genotype
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Skin / pathology*


  • Autoantibodies
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Cytokines