IL-7Rα glutamylation and activation of transcription factor Sall3 promote group 3 ILC development.
IL-7Rα glutamylation and activation of transcription factor Sall3 promote group 3 ILC development.
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IL-7R α谷氨酰化和转录因子Sall3的激活促进第3组ILC的发育
DOI：
10.1038/s41467-017-00235-x
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发表时间：
2017-08-10
影响因子：
16.6
通讯作者：
Fan Z
中科院分区：
文献类型：
--
作者：
Liu B;Ye B;Zhu X;Huang G;Yang L;Zhu P;Du Y;Wu J;Meng S;Tian Y;Fan Z
第3组天然淋巴样细胞(ILC3)促进淋巴器官生成，增强抗细菌感染的免疫应答。然而，ILC3细胞是如何发育和维持的仍不清楚。在这里，我们发现羧基肽酶CCP2在常见的辅助性先天淋巴祖细胞中高表达，CCP2缺乏会增加ILC3的数量。白细胞介素7受体亚单位α(IL-7Rα)被认为是α脱谷氨化的底物，在常见的辅助性先天淋巴祖细胞中，IL-7R CCP的多谷氨酰化是由多谷氨酸酶TTLL4和TTLL13催化的。IL-7Rα多谷氨酸化激活STAT5启动转录因子sAL3在常见的辅助性先天淋巴祖细胞中的表达，从而促进ILC3细胞的分化。此外，Ttl14−/−或Ttl13−/−小鼠还降低了常见辅助性先天淋巴祖细胞的IL-7Rα多谷氨酸化和sALL3的表达。重要的是，携带IL-7RαE446A突变的小鼠降低了Sall3的表达和ILC3的数量。因此，IL-7Rα的多谷氨酰化和去谷氨酸化密切控制着ILC3s的发育和效应功能。先天淋巴样细胞(ILC)是黏膜免疫的重要调节细胞，但其发育和动态平衡的调节机制尚不清楚。作者认为，第3组ILCs的分化受IL-7Rα的谷氨酸化和转录因子Sall3的诱导所控制。
Group 3 innate lymphoid cells (ILC3) promote lymphoid organogenesis and potentiate immune responses against bacterial infection. However, how ILC3 cells are developed and maintained is still unclear. Here, we show that carboxypeptidase CCP2 is highly expressed in common helper-like innate lymphoid progenitors, the progenitor of innate lymphoid cells, and CCP2 deficiency increases ILC3 numbers. Interleukin-7 receptor subunit alpha (IL-7Rα) is identified as a substrate of CCP2 for deglutamylation, and IL-7Rα polyglutamylation is catalyzed by polyglutamylases TTLL4 and TTLL13 in common helper-like innate lymphoid progenitors. IL-7Rα polyglutamylation triggers STAT5 activation to initiate transcription factor Sall3 expression in common helper-like innate lymphoid progenitors, which drives ILC3 cell differentiation. Moreover, Ttll4 −/− or Ttll13 −/− mice have reduced IL-7Rα polyglutamylation and Sall3 expression in common helper-like innate lymphoid progenitors. Importantly, mice with IL-7Rα E446A mutation have reduced Sall3 expression and ILC3 population. Thus, polyglutamylation and deglutamylation of IL-7Rα tightly controls the development and effector functions of ILC3s. Innate lymphoid cells (ILC) are important regulators of mucosal immunity, but how their development and homeostasis are modulated is still unclear. Here the authors show that the differentiation of group 3 ILCs is controlled by the glutamylation of IL-7Rα and the induction of transcription factor Sall3.
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影响因子：
64.5
作者：
Garnham CP;Vemu A;Wilson-Kubalek EM;Yu I;Szyk A;Lander GC;Milligan RA;Roll-Mecak A
通讯作者：
Roll-Mecak A
影响因子：
32.4
作者：
Diefenbach, Andreas;Colonna, Marco;Koyasu, Shigeo
通讯作者：
Koyasu, Shigeo
影响因子：
32.4
作者：
Guo, Xiaohuan;Qiu, Ju;Tu, Tony;Yang, Xuanming;Deng, Liufu;Anders, Robert A.;Zhou, Liang;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
影响因子：
32.4
作者：
Bernink, Jochem H.;Krabbendam, Lisette;Spits, Hergen
通讯作者：
Spits, Hergen
影响因子：
56.9
作者：
EDDE, B;ROSSIER, J;DENOULET, P
通讯作者：
DENOULET, P