Activation of the interleukin-23/interleukin-17 signalling pathway in autoinflammatory and autoimmune uveitis.Prog Retin Eye Res. 2020 May 16 [Online ahead of print]PR
Uveitis is a group of diseases characterized by intraocular inflammation, of which some are driven by autoinflammatory or autoimmune responses, such as Vogt-Koyanagi-Harada disease, Behçet's disease, uveitis associated with spondyloarthritis, ocular sarcoidosis, sympathetic ophthalmia and birdshot chorioretinopathy. These entities have various clinical forms, but genetic and biomarker data suggest that they share a common molecular basis, activation of the Interleukin (IL)-23/IL-17 pathway. Multiple factors including genetic predisposition, various cytokine imbalances, infectious agents and gut alterations are found to trigger an aberrant response of this pathway. The enhanced activity of the IL-23/IL-17 pathway is committed to the expansion and pathogenicity of Th17 cells. Evidence from animal models demonstrates that the development of pathogenic Th17 cells is responsible for the induction of experimental autoimmune uveitis. Further findings indicate that retinal pigment epithelium (RPE) cells may be a target of IL-17. IL-17 triggers downstream inflammatory cascades and causes dysfunction of RPE cells, which may affect retinal barrier function and thereby promote intraocular inflammation. Currently, several emerging drugs blocking the IL-23/IL-17 pathway have been assessed for the treatment of uveitis in pilot studies. The purpose of this is to summarize updated biological knowledge and preliminary clinical data, providing the rationale for further development and evaluation of novel drugs targeting the IL-23/IL-17 pathway in autoinflammatory and autoimmune uveitis. Future studies may focus on translational medicine targeting the IL-23/IL-17 pathway for the improvement of diagnosis and treatment of uveitis. In conclusion, activation of the IL-23/IL-17 pathway is a critical biological event and can be an important target for the treatment of autoinflammatory and autoimmune uveitis.