TSLP AhR IAId Tryptophan Epidermis Dermis AhRE TSLP IL-4,IL-5,IL-13,IL-22AD Background: Previous studies have revealed significant alterations in the skin microbiota of patients with atopic dermatitis (AD) not only in diversity and composition but also in function, and the tryptophan (Trp) metabolic pathway is attenuated in the skin microbiota of patients with AD. Objective: We sought to assess Trp metabolites on the skin surfaces of patients with AD and to explore the function of the microbial Trp metabolites in skin inflammation in patients with AD.Methods: A gel-patch method was developed to collect metabolites on the skin surface, which were then assessed by using liquid chromatography-tandem mass spectrometry. A mouse model of calcipotriol (MC903)-induced AD-like dermatitis was used to evaluate the effects of microbial metabolites on AD, and aryl hydrocarbon receptor (AhR)-null mice and keratinocyte cultures were used to investigate the mechanism.We thank Professor Shau-Ku Huang for helpful suggestions and reviewing the manuscript. Key messagesd Levels of microbial metabolites of Trp metabolism on skin surfaces of patients with AD were lower than those of healthy subjects.d IAId significantly attenuated skin inflammation in a mouse model of MC903-induced AD-like dermatitis.d IAId inhibited TSLP expression in keratinocytes in an AhR-dependent manner.

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PlxnB2 and its ligand, CD100, were originally identified as axon-guidance molecules that function during neuronal development; however, studies also showed that CD100-plexins participate in various immune responses. In this study, we found that the expression of PlxnB2 on keratinocytes was specifically increased in lesional skin of psoriasis patients but not atopic dermatitis. Levels of soluble CD100 and membrane-bound CD100 were elevated in sera of psoriasis patients and on keratinocytes of psoriatic skin, respectively. By binding to PlxnB2, soluble CD100 promoted the production of CXCL-1, CCL-20, IL-1β, and IL-18 by keratinocytes and activated the NLRP3 inflammasome. Moreover, CD100-PlxnB2 stimulated the NF-κB signaling pathway in keratinocytes through activation of small GTPase RhoA and Rac1. Our data showed that cooperation of CD100 and PlxnB2 promoted the inflammatory responses in keratinocytes by activating NF-κB and the NLRP3 inflammasome and participated in the pathogenesis of psoriasis. CD100/PlxnB2 might be a potential therapeutic target for psoriasis.