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Publication : SRC3 Is a Cofactor for RORγt in Th17 Differentiation but Not Thymocyte Development.

First Author  He Z Year  2019
Journal  J Immunol Volume  202
Issue  3 Pages  760-769
PubMed ID  30567733 Mgi Jnum  J:270102
Mgi Id  MGI:6274823 Doi  10.4049/jimmunol.1801187
Citation  He Z, et al. (2019) SRC3 Is a Cofactor for RORgammat in Th17 Differentiation but Not Thymocyte Development. J Immunol 202(3):760-769
abstractText  SRC3, a highly conserved member of the steroid receptor coactivator (SRC) family, is recruited by transcription factors to regulate cellular function. Previously, we demonstrated that SRC1, another highly conserved member of the SRC family, interacts with RORgammat to regulate Th17 differentiation. However, the relationship between SRC1 and SRC3 in the regulation of Th17 cell function remains unknown. In this study, we demonstrate that mouse SRC3 interacts with RORgammat in Th17 cells but not in thymocytes. In addition, Src3(-/-) mice exhibited defective Th17 differentiation and induction of experimental autoimmune encephalomyelitis but normal thymocyte development. Furthermore, a K313 to arginine mutation of RORgammat (RORgammat-K313R), which disrupts the interaction of RORgammat with SRC3 but not with SRC1, impairs Th17 differentiation but not thymocyte development. These data suggest that SRC3 works with SRC1 to regulate RORgammat-dependent Th17 differentiation but is not essential for RORgammat-dependent thymocyte development.
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