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Published on: November 15, 2024
RORγt protein modifications and IL-17-mediated inflammation
Ritesh Kumar1, Arianne L Theiss2, K Venuprasad1
1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Immunology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Abstract:
RORγt, the master transcription factor for cytokine interleukin (IL)-17, is expressed explicitly in Th17 cells, γδT 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 RORγt-IL-17 axis has been the focus of intense research. Recently, several studies have shown that RORγt is modified by multiple post-translational mechanisms, including ubiquitination, acetylation, SUMOylation, and phosphorylation. This review discusses how post-translational modifications modulate RORγt 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 RORγt+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.
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