Abstract
Abstract RORgt controls the differentiation of TH17 cells involved in autoimmunity such as experimental autoimmune encephalomyelitis (EAE). RORgt also regulates thymocyte development and lymph node genesis. Here we show sumoylation as a novel mechanism to regulate RORgt function. Loss of Sumo3, but not Sumo1, dampens TH17 differentiation and delays the progression of thymic immature CD8+cells (ISP). RORgt is SUMO3-modified at lysine 31 (K31), and mutation of K31 to arginine (RORgtK31R) in mice to prevent sumoylation impairs RORgt-dependent function including defective TH17 differentiation, resistance to TH17-mediated EAE, accumulation of thymic ISP and lack of Peyer’s patches. Mechanically, RORgt-K31 sumoylation stabilizes the binding of SRC1 through recruiting histone acetyltransferase KAT2A. Lastly, E3 ligase PIAS4 binds and sumoylates RORgt at K31, and regulates RORgt-dependent TH17 differentiation and progression of thymic ISP. This study thus demonstrates sumoylation as a critical mechanism for regulating RORgt function, and reveal new drug targets for preventing TH17-mediated autoimmunity.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
