Murine sclerodermatous chronic graft-versus-host disease (ScI-cGVHD) is established by transplantation of B10.D2 bone marrow and splenocytes into sublethally irradiated BALB/c recipients as an animal model for human ScI-cGVHD and systemic sclerosis (SSc). the authors investigated the effects of FTY (fingolimod) that is a potent immunomodulatory drug in relation to murine ScI-cGVHD. FTY was orally administered to allogeneic recipients at a dose of 1 mg/kg from the day of bone marrow transplantation (BMT). FTY treatment inhibited ScI-cGVHD severity and fibrosis.FTY induced expansion of splenic myeloidderived suppressor cells at 7 days after BMT, regulatory T cells and regulatory B cells at 14 days after BMT and inhibition of skin CD4+T cell, CDS+T cell, and CD11b+ cell infiltration by flow cytometric analysis. Moreover, FTY diminished mRNA expression of chemokine/cytokine in the skin. FTY suppresses immune response by promoting expand of regulatory cells and reduces the infiltration of immune cells into skin. Therefore, these results have important implication for the potential treatment of FTY in ScI-cGVHD and SSc in human.
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