D-mannose blocks the interaction between keratinocytes and Th17 cells to alleviate psoriasis by inhibiting HIF-1?/CCL20 in mice

Psoriasis is an autoimmune chronic inflammatory skin disease with an unclear pathogenesis that is difficult to cure, causing serious physical and mental burdens for patients. Previous research showed that a mutually reinforcing vicious cycle caused by keratinocytes (KC) and a variety of immune cells plays an important role in psoriatic inflammation. D-Mannose, a widely distributed metabolite in the body, has been found to treat several metabolic diseases, but its impact on psoriasis remains unknown. Our study aims to investigate the effects of Dmannose on psoriasis and its specific mechanism. Here, we found that D-mannose alleviates psoriasis in mice both as oral and topical agents. Specifically, D-mannose down-regulated the expression of hypoxia-inducible factor 1A (HIF-1 alpha) and inhibited the expression of chemokine CCL20 in keratinocytes, thereby inhibiting the local infiltration of Th17 cells and breaking the cycle of keratinocytes-Th17 cells. Overall, our study indicates that Dmannose alleviates cutaneous inflammation in psoriasis by inhibiting the HIF-1 alpha/CCL20/Th17 cells axis, and Dmannose has the potential to be used as an oral and topical agent in the treatment of psoriasis.