Canthaxanthin ameliorates atopic dermatitis in mice by suppressing Th2 immune response.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by intense pruritus and complex immunopathogenic mechanisms. Recent evidence has highlighted the critical link between dysregulated intestinal microecology and altered immune responses in AD progression. As essential components of the intestinal microenvironment, metabolites play pivotal roles in various physiological processes. Through metabolomic profiling in an AD mouse model, we identified a significant reduction in canthaxanthin (CTX), a bacterial-derived metabolite naturally present in many foods, in AD mice compared to healthy controls. To investigate the therapeutic potential of CTX, we established an AD model by repeatedly applying 2,4-dinitrochlorobenzene (DNCB) to the ears and dorsal skin of mice, successfully inducing AD-like symptoms and lesions. Notably, oral administration of CTX significantly attenuated skin inflammation and reduced serum IgE levels in this DNCB-induced AD model. Both in vivo and in vitro studies demonstrated that CTX treatment effectively suppressed Th2 immune responses. Mechanistically, we found that CTX significantly inhibited the activation of the JAK2-STAT6 signaling pathway in Th2-polarized T cells. Our findings not only demonstrate the therapeutic efficacy of CTX in AD but also elucidate its molecular mechanism in modulating T helper cell subset balance. These insights suggest that CTX could serve as a promising therapeutic agent for AD and potentially other Th2 response-mediated immune disorders.