The Transcription Factor ThPOK Regulates ILC3 Lineage Homeostasis and Function During Intestinal Infection.
The Transcription Factor ThPOK Regulates ILC3 Lineage Homeostasis and Function During Intestinal Infection.
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转录因子 ThPOK 在肠道感染期间调节 ILC3 谱系稳态和功能
DOI：
10.3389/fimmu.2022.939033
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wang, Lie
中科院分区：
文献类型：
--
作者：
Gao, Xianzhi;Shen, Xin;Liu, Kuai;Lu, Chenyu;Fan, Ying;Xu, Qianying;Meng, Xiaoyu;Hong, Shenghui;Huang, Zhengwei;Liu, Xia;Lu, Linrong;Wang, Lie
先天性淋巴样细胞（inate lymphoid cells，ILC）是一种异质性的淋巴细胞，具有适应性T细胞的细胞因子和转录特征。关键转录因子之间的动态平衡决定了ILC亚群的异质性、可塑性和功能。转录因子ThPOK在生物进化中高度保守，在T细胞分化中发挥关键作用。然而，ThPOK在ILC 3中的功能尚未被确定。在这里，我们发现ThPOK调节ILC 3s的稳态，因为缺乏ThPOK的小鼠显示NKp 46 + ILC 3s减少和CCR 6-NKp 46-ILC 3s增加。ThPOK缺陷小鼠对S.由于NKp 46 + ILC 3的IFN-γ分泌受损，鼠伤寒杆菌感染。此外，ThPOK参与ILC 3介导的C.啮齿动物感染的IL-17 A分泌负调节。ThPOK通过抑制RORγt（其间接释放T-bet表达）来保留NKp 46 + ILC 3的身份。在分子水平上，ThPOK直接与Rorc和IL 23 r结合以抑制其表达，从而进一步调节IL-17 A的分泌。总的来说，我们的分析揭示了ThPOK在ILC 3亚群的稳态和功能中的关键作用。
Innate lymphoid cells (ILCs) have been identified as a heterogeneous population of lymphocytes that mirrors the cytokine and transcriptional profile of adaptive T cells. The dynamic balance between key transcription factors determines the heterogeneity, plasticity, and functions of ILC subsets. The transcription factor ThPOK is highly conserved in biological evolution and exerts pivotal functions in the differentiation of T cells. However, the function of ThPOK in ILC3s has not been identified. Here, we found that ThPOK regulated the homeostasis of ILC3s, as mice lacking ThPOK showed decreased NKp46+ ILC3s and increased CCR6- NKp46- ILC3s. ThPOK-deficient mice were more sensitive to S. typhimurium infection due to the impaired IFN-γ secretion of NKp46+ ILC3s. Furthermore, ThPOK participates in ILC3-mediated control of C. rodentium infection by negatively regulating IL-17A secretion. ThPOK preserves the identity of NKp46+ ILC3s by repressing RORγt, which indirectly releases T-bet expression. On the molecular level, ThPOK directly binds to Rorc and Il23r to restrain their expression which further modulates IL-17A secretion. Collectively, our analysis revealed a critical role of ThPOK in the homeostasis and functions of ILC3 subsets.
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DOI：
10.1073/pnas.91.20.9372
发表时间：
1994-09-27
影响因子：
11.1
作者：
GALERA, P;MUSSO, M;KARSENTY, G
通讯作者：
KARSENTY, G
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：
64.5
作者：
Kouros-Mehr, Hosein;Slorach, Euan M.;Werb, Zena
通讯作者：
Werb, Zena
影响因子：
30.5
作者：
Lee, Jacob S.;Cella, Marina;McDonald, Keely G.;Garlanda, Cecilia;Kennedy, Gregory D.;Nukaya, Manabu;Mantovani, Alberto;Kopan, Raphael;Bradfield, Christopher A.;Newberry, Rodney D.;Colonna, Marco
通讯作者：
Colonna, Marco
干扰素-γ和先天淋巴样细胞在先天和适应性免疫细胞介导的肠炎中的作用。
影响因子：
7.3
作者：
Brasseit J;Kwong Chung CKC;Noti M;Zysset D;Hoheisel-Dickgreber N;Genitsch V;Corazza N;Mueller C
通讯作者：
Mueller C