Identification of a Long Noncoding RNA TRAF3IP2-AS1 as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, , regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene that is homologous to and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.