A two-amino-acid substitution in the transcription factor RORγt disrupts its function in T(H)17 differentiation but not in thymocyte development.
A two-amino-acid substitution in the transcription factor RORγt disrupts its function in T(H)17 differentiation but not in thymocyte development.
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DOI：
10.1038/ni.3832
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发表时间：
2017-10
影响因子：
30.5
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
He Z;Ma J;Wang R;Zhang J;Huang Z;Wang F;Sen S;Rothenberg EV;Sun Z
RORγt调节TH17分化、胸腺T细胞发育和淋巴结发生。虽然RORγt的消除可以阻止th17介导的实验性自身免疫性脑脊髓炎（EAE），但它也会破坏胸腺细胞的发育，从而导致致命的胸腺淋巴瘤。在这里，我们发现了RORγt （RORγtM）中的两个氨基酸突变，它们优先破坏TH17的分化，而不是胸腺细胞的发育。表达rorγ - tm的小鼠对与TH17分化缺陷相关的EAE具有抗性，但除了Peyer 's斑块外，胸腺细胞发育和淋巴结形成保持正常。ror γ - tm显示K69位点泛素化减少，这是TH17分化而不是T细胞发育所选择性需要的。这项研究将为选择性靶向th17介导的自身免疫，但不影响胸腺细胞发育和诱导淋巴瘤的治疗方法的发展提供信息。
RORγt regulates TH17 differentiation, thymic T cell development and lymph node genesis. Although elimination of RORγt prevents TH17-mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified two amino acid mutations in RORγt (RORγtM) that preferentially disrupted TH17 differentiation but not thymocyte development. Mice expressing RORγtM were resistant to EAE associated with defective TH17 differentiation, but maintained normal thymocyte development and lymph node genesis, except for Peyer’s patches. RORγtM showed reduced ubiquitination at K69 that is selectively required for TH17 differentiation but not T cell development. This study will inform the development of treatments that selectively target TH17-mediated autoimmunity, but do not affect thymocyte development and induce lymphoma.
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影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1126/science.aaa4282
发表时间：
2015-08-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Okada S;Markle JG;Deenick EK;Mele F;Averbuch D;Lagos M;Alzahrani M;Al-Muhsen S;Halwani R;Ma CS;Wong N;Soudais C;Henderson LA;Marzouqa H;Shamma J;Gonzalez M;Martinez-Barricarte R;Okada C;Avery DT;Latorre D;Deswarte C;Jabot-Hanin F;Torrado E;Fountain J;Belkadi A;Itan Y;Boisson B;Migaud M;Arlehamn CSL;Sette A;Breton S;McCluskey J;Rossjohn J;de Villartay JP;Moshous D;Hambleton S;Latour S;Arkwright PD;Picard C;Lantz O;Engelhard D;Kobayashi M;Abel L;Cooper AM;Notarangelo LD;Boisson-Dupuis S;Puel A;Sallusto F;Bustamante J;Tangye SG;Casanova JL
通讯作者：
Casanova JL
影响因子：
32.4
作者：
Jain, Renu;Chen, Yi;Cua, Daniel J.
通讯作者：
Cua, Daniel J.
影响因子：
64.5
作者：
Dang EV;Barbi J;Yang HY;Jinasena D;Yu H;Zheng Y;Bordman Z;Fu J;Kim Y;Yen HR;Luo W;Zeller K;Shimoda L;Topalian SL;Semenza GL;Dang CV;Pardoll DM;Pan F
通讯作者：
Pan F