| First Author | He Z | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 10 | Pages | 1128-1138 |
| PubMed ID | 28846085 | Mgi Jnum | J:248565 |
| Mgi Id | MGI:6095516 | Doi | 10.1038/ni.3832 |
| Citation | He Z, et al. (2017) A two-amino-acid substitution in the transcription factor RORgammat disrupts its function in TH17 differentiation but not in thymocyte development. Nat Immunol 18(10):1128-1138 |
| abstractText | The transcription factor RORgammat regulates differentiation of the TH17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORgammat prevents TH17 cell-mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORgammat (RORgammat(M)) that 'preferentially' disrupted TH17 differentiation but not thymocyte development. Mice expressing RORgammat(M) were resistant to EAE associated with defective TH17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORgammat(M) showed less ubiquitination at Lys69 that was selectively required for TH17 differentiation but not T cell development. This study will inform the development of treatments that selectively target TH17 cell-mediated autoimmunity but do not affect thymocyte development or induce lymphoma. |
