@article{oai:nagasaki-u.repo.nii.ac.jp:00015920,
 author = {Komura, Kazuhiro and Fujimoto, M and Yanaba, Koichi and Matsushita, Takeji and Matsushita, Y and Horikawa, Mayuka and Ogawa, Fumihide and Shimizu, K and Hasegawa, M and Takehara, K and Sato, Shinichi},
 issue = {6},
 journal = {Annals of the rheumatic diseases},
 month = {Jun},
 note = {OBJECTIVE: To assess the association of CD40/CD40 ligand (CD40L) interactions with the development of skin fibrosis and autoimmunity in tight-skin (TSK/+) mouse, which is a mouse model for human systemic sclerosis. METHODS: Newly born TSK/+ mice were treated with murine anti-CD40L monoclonal antibody (100 microg intraperitoneally weekly). Hypodermal thickness of 8-week-old female mice (defined as the thickness of a subcutaneous loose connective tissue layer beneath the panniculus carnosus) was measured under a light microscope. All skin sections were taken from the para-midline, upper back region. Serum anti-topoisomerase I autoantibody levels, serum immunoglobulin levels and plasma soluble CD40L levels were determined by enzyme-linked immunosorbent assay. For analysis of lymphocyte surface molecules, single cell suspensions of lymphocytes were stained by monoclonal antibodies. Proliferation of TSK/+ B cells and fibroblasts to anti-CD40 antibodies was assessed by the uptake of [3H]-labelled thymidine and bromodeoxyuridine, respectively. RESULTS: The blockade of CD40/CD40L interactions by anti-CD40L monoclonal antibody significantly reduced cutaneous fibrosis (65%) and anti-topoisomerase I autoantibody in TSK/+ mice. Anti-CD40L monoclonal antibody also normalised B lymphocyte abnormal activation in TSK/+ mice, demonstrated by hyper-gamma-globulinaemia. Furthermore, augmented CD40/CD40L interactions in TSK/+ mice were suggested by upregulated expression of CD40L on CD4(+) T cells, elevated plasma soluble CD40L levels. The hyperresponsiveness to CD40 stimulation was also observed in TSK/+ B cells and fibroblasts. CONCLUSIONS: Cutaneous fibrosis and autoimmunity in TSK/+ mice are closely correlated with CD40/CD40L interactions., Annals of the rheumatic diseases, 67(6), pp.867-872; 2008},
 pages = {867--872},
 title = {Blockade of CD40/CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse.},
 volume = {67},
 year = {2008}
}