Sphingosine-1-phosphate (S1P) and its receptors have been implicated in atopic dermatitis. S1P
2
was found to function as a pro-allergic receptor, while its antagonist JTE-013 was found to suppress allergic asthma in mice. Topical application of JTE-013 has not been investigated in an
in vivo
model of atopic dermatitis. Therefore, the therapeutic potential of JTE-013 topical application was evaluated by the use of a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. DNCB-induced inflammation and mast cell accumulation in skin tissues were significantly suppressed by topical JTE-013 treatment in BALB/c mice. DNCB-induced increase of lymph nodes sizes and elevated inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in lymph nodes were also significantly reduced by the JTE-013 treatment. Elevated serum levels of IgE were significantly suppressed by the topical treatment of JTE-013. In summary, the topical treatment of JTE-013 S1P
2
antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous patches or plaques with a complex etiology (Davidson et al., 2019). Atopic dermatitis affects up to 20% of children worldwide and can significantly impair the quality of life owing to emotional distress, sleep disruption, and social awkwardness (Leung and Guttman-Yassky, 2017). Gut microbiota produce dietary metabolites such as short-chain fatty acids, which exert antiinflammatory effects (Trompette et al., 2014). Free fatty acid receptor 2 (FFA2, formerly known as GPR43) is a specific receptor for short-chain fatty acids such as acetate, propionate, and butyrate (
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