Yogurt Alleviates Imiquimod-Induced Psoriasis by Activating the Lactate/GPR81 Signaling Axis in Mice

In addition to colorectal cancer and metabolic syndrome, regular yogurt consumption has shown promise in improving skin inflammation. In this study, we investigated the effects and possible mechanisms of yogurt on imiquimod-induced psoriasis-like inflammation in mice. After oral administration with yogurt (18 or 36 g/kg) and/or its main metabolite lactate (250 or 500 mg/kg) for 3 days, the mice were treated with a topical dose of 62.5 mg of imiquimod (IMQ) cream for seven consecutive days. Data showed that yogurt and lactate treatment significantly reduced the severity of psoriasis-like skin lesions, excessive keratinocyte proliferation, and immune cell infiltration. Mechanistically, we found that the genetic deficiency of the lactate receptor GPR81 aggravated psoriasis-like features in mice. Activation of the lactate/GPR81 axis inhibited the degradation of IκBα, prevented the nuclear translocation of histone deacetylase 3 (HDAC3) in macrophages, and thus constrained skin inflammation. Overall, these findings suggest that yogurt consumption effectively protects against experimental psoriasis and targeting the lactate/GPR81 signaling axis could be a promising approach for psoriasis inflammation management.