In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-01-24)
Abstract:
Sphingosine-1-phosphate (S1P), a lipid mediator, regulates lymphocyte migration between lymphoid tissue and blood. Furthermore, S1P participates in several physiological phenomena including angiogenesis, inflammation, immune regulation, and neurotransmitter release. Moreover, S1P/S1P receptor signaling involves in systemic sclerosis (SSc) pathogenesis. This study aimed to investigate whether the selective S1P 1 receptor modulator cenerimod attenuates murine sclerodermatous models. Cenerimod was orally administered to murine sclerodermatous chronic graft versus host disease (Scl-cGVHD) mice, either from day 0 to 42 or day 22 to 42 after bone marrow transplantation. Bleomycin-induced SSc model mice were administered cenerimod from day 0 to 28. Early cenerimod administration inhibited, and delayed cenerimod administration attenuated skin and lung fibrosis in Scl-cGVHD mice. Cenerimod suppressed the infiltration of CD4 + T cells, CD8 + T cells, and CD11b + cells into the inflamed skin of Scl-cGVHD mice as opposed to control mice. In contrast, cenerimod increased the frequency of regulatory T cells in the spleen and skin of Scl-cGVHD mice. Additionally, cenerimod attenuated the mRNA expression of extracellular matrix and fibrogenic cytokines in the skin. Furthermore, cenerimod attenuated bleomycin-induced fibrosis in the skin and lung. Hence, the selective S1P 1 receptor modulator cenerimod is a promising candidate for treating patients with SSc and Scl-cGVHD.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-37074-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2019
detail.hit.zdb_id:
2615211-3
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