RORγt protein modifications and IL-17-mediated inflammation

ROR gamma t, the master transcription factor for cytokine interleukin (IL)-17, is expressed explicitly in Th17 cells, gamma delta T cells, and type 3 innate lymphoid cells in mice and humans. Since dysregulated IL-17 expression is strongly linked to several human inflammatory diseases, the ROR gamma t-IL-17 axis has been the focus of intense research. Recently, several studies have shown that ROR gamma t is modified by multiple post-translational mechanisms, including ubiquitination, acetylation, SUMOylation, and phosphorylation. This review discusses how post-translational modifications modulate ROR gamma t function and its turnover to regulate IL-17-driven inflammation. Broad knowledge of these pathways is crucial for a clear understanding of the pathogenic role of ROR gamma t+IL-17+ cells and for the development of putative therapeutic strategies to target IL-17-driven diseases such as multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.