Indole-3-Lactic Acid Inhibits Keratinocyte Proliferation Through the Aryl Hydrocarbon Receptor in Psoriasis

Psoriasis is a chronic inflammatory skin disease whose pathogenesis involves dysregulation of the skin microbiota. Multiple studies have revealed alterations in microbial community composition between psoriatic lesions and healthy skin. However, the metabolic pathways of the skin microbiota, particularly those involving tryptophan metabolism, remain poorly understood. In this study, we employed an imiquimod (IMQ)-induced psoriasis-like dermatitis and found that the primary indole derivative of tryptophan metabolism, indole-3-lactic acid (ILA), significantly alleviated epidermal hyperproliferation as evidenced by reduced expression of proliferation-associated keratins K6, K16, and K17 in an AhR-dependent manner. Furthermore, using AhR knockout mice combined with the IMQ application, we observed that AhR deficiency markedly exacerbated disease severity and increased keratinocyte proliferation. Collectively, our findings suggest that ILA exerts protective effects against psoriasis development through an AhR-dependent mechanism, negatively regulating the expression of K6, K16, and K17, thereby inhibiting keratinocyte proliferation and alleviating the pathogenic progression of psoriasis.