The transcription factor RORγt regulates differentiation of the T_H17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents T_H17 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 RORγt (RORγt^M) that 'preferentially' disrupted T_H17 differentiation but not thymocyte development. Mice expressing RORγt^M were resistant to EAE associated with defective T_H17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORγt^M showed less ubiquitination at Lys69 that was selectively required for T_H17 differentiation but not T cell development. This study will inform the development of treatments that selectively target T_H17 cell–mediated autoimmunity but do not affect thymocyte development or induce lymphoma.

中文翻译：

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转录因子RORγt中的两个氨基酸取代破坏了其在TH17分化中的功能，但没有破坏胸腺细胞的发育

转录因子ROR γ吨T形时调节分化_ħ辅助T细胞，胸腺T细胞的发育和淋巴结成因的17子集。虽然消除ROR的γ吨防止Ť _ħ 17细胞介导的实验性自身免疫性脑脊髓炎（EAE），它会破坏胸腺细胞发育，这可能导致致命的胸腺淋巴瘤。在这里，我们确定了ROR两氨基酸替换γ吨（ROR γ吨^中号），该“优先”打乱Ť _ħ 17分化但不是胸腺细胞发育。表达ROR小鼠γ吨^中号进行到EAE有抗性的缺陷相关联Ť _ħ17分化，但维持正常的胸腺细胞发育和正常的淋巴结发生，除了派伊尔氏斑。ROR γ吨^中号在该被选择性需要对于T Lys69显示出较少的泛素化_ħ 17分化但不是T细胞发育。这项研究将为选择性靶向T _H 17细胞介导的自身免疫但不影响胸腺细胞发育或诱发淋巴瘤的治疗方法的开发提供信息。