TY - JOUR
T1 - RORγt protein modifications and IL-17-mediated inflammation
AU - Kumar, Ritesh
AU - Theiss, Arianne L.
AU - Venuprasad, K.
N1 - Funding Information:
The authors thank Dr Ezra Burstein for the helpful discussions and Dr Wayne Lancaster for the critical reading of the manuscript. This work was supported by funds from the National Institutes of Health ( R01-DK115668 , R01-AI155786 ) and Cancer Prevention Research Institute of Texas ( RP160577 , RP190527 ), and a translational pilot project grant from the Harold C. Simmons Comprehensive Cancer Center , UT Southwestern Medical Center ( 23001045 ) to K.V. and R01-DK117001 to K.V. and A.L.T.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - IL-17
KW - RORγt
KW - Th17
KW - autoimmune diseases
KW - post-translational modifications
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U2 - 10.1016/j.it.2021.09.005
DO - 10.1016/j.it.2021.09.005
M3 - Review article
C2 - 34635393
AN - SCOPUS:85116683093
SN - 1471-4906
VL - 42
SP - 1037
EP - 1050
JO - Trends in Immunology
JF - Trends in Immunology
IS - 11
ER -