The investigation of selective sphingosine-1 phosphate receptor 1&4 modulator to treat alopecia areata mouse model 2881

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Abstract Description Alopecia areata (AA) is a T cell mediated autoimmune disease characterized phenotypically by hair loss. NKG2D+ CD8+ T cells is involved in the pathogenesis of AA. Sphingosine-1 phosphate (S1P) is a biologically active metabolite of cell membrane sphingolipids, which is essential for immune cell transport, and is known to be mainly involved in immune and inflammatory reactions. Due to involvement of S1P receptor (S1PR) in the immune system, S1PR modulator is being investigated for application in multiple sclerosis and other conditions. Among the five S1PRs, S1PRs 1&4 modulator was used to confirm its efficacy in the treatment of AA. AA lesion size measurement, disease-free ratio, immunohistochemistry, flow cytometry and bulk RNA-sequencing were used for analysis method. After oral administration of S1PRs 1&4 modulator for 12 weeks to AA mice, it was confirmed that the AA lesion area and disease-free ratio were significantly decreased compared to control group, and there was a tendency for the infiltration of CD8+ T cells in the lesion skin to decrease. Furthermore, a decrease in NKG2D levels was observed in effector CD8+ T cells, and through bulk RNA-sequencing, a reduction in receptor internalization and cytotoxicity at the transcriptome level was confirmed. According to this result, we speculate that S1PR 1&4 modulator can be used as a promising treatment for AA. Funding Sources This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. RS-2024-00349612) Topic Categories Therapeutic Approaches to Autoimmunity (THER)

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