BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection.
BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection.
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DOI：
10.1126/sciimmunol.abc9934
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发表时间：
2022-01-14
影响因子：
24.8
通讯作者：
Cui, Weiguo
中科院分区：
文献类型：
--
作者：
Wu, Xiaopeng;Kasmani, Moujtaba Y.;Zheng, Shikan;Khatun, Achia;Chen, Yao;Winkler, Wendy;Zander, Ryan;Burns, Robert;Taparowsky, Elizabeth J.;Sun, Jie;Cui, Weiguo
活化的第2组先天淋巴样细胞（ILC 2）在宿主防御急性呼吸道病毒感染中积累并促进炎症消退和组织修复。然而，肺中ILC 2的异质性和ILC 2细胞促进组织修复的机制仍然难以捉摸。使用单细胞RNA测序（scRNA-seq），我们确定了一个转录上不同的ILC 2子集，该子集显示了伤口愈合标记基因和转录因子BATF的富集。值得注意的是，BATF促进ILC 2的增殖和功能，并在流感病毒感染期间限制其可塑性。在缺乏BATF的情况下，ILC 2失去其免疫保护特性并获得致病性ILC 3样功能，导致持续的中性粒细胞浸润、组织损伤和呼吸衰竭。在机制上，BATF直接结合到伤口愈合基因的顺式调控元件，维持其染色质可及性，并促进其表达。最后，BATF在支持ILC 2细胞身份和功能的IL-33-ST 2前馈回路中起重要作用。总的来说，我们的研究结果揭示了BATF依赖的ILC 2程序，从而为终止急性病毒感染期间的有害炎症提供了潜在的治疗靶点。BATF调节急性呼吸道病毒感染期间ILC 2介导的组织修复和炎症消退
Activated group 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, the heterogeneity of ILC2s in the lung and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identify a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promotes the proliferation and function of ILC2s and restricts their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lose their immune protective properties and acquire pathogenic ILC3-like functions, leading to persistent neutrophil infiltration, tissue damage, and respiratory failure. Mechanistically, BATF directly binds to the cis-regulatory elements of wound healing genes, maintains their chromatin accessibility, and promotes their expression. Lastly, BATF plays an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program, thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection. BATF regulates ILC2-mediated tissue repair and inflammation resolution during acute respiratory virus infection.
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影响因子：
32.4
作者：
Colonna M
通讯作者：
Colonna M
影响因子：
8
作者：
Califano D;Furuya Y;Roberts S;Avram D;McKenzie ANJ;Metzger DW
通讯作者：
Metzger DW
产生 IL-17 ST2( ) 2 组先天淋巴细胞在肺部炎症中发挥致病作用
DOI：
10.1016/j.jaci.2018.03.007
发表时间：
2019-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Cai T;Qiu J;Ji Y;Li W;Ding Z;Suo C;Chang J;Wang J;He R;Qian Y;Guo X;Zhou L;Sheng H;Shen L;Qiu J
通讯作者：
Qiu J
影响因子：
3.3
作者：
Franco, Jovany J.;Atieh, Youmna;Eisenhoffer, George T.
通讯作者：
Eisenhoffer, George T.
影响因子：
32.4
作者：
Califano D;Cho JJ;Uddin MN;Lorentsen KJ;Yang Q;Bhandoola A;Li H;Avram D
通讯作者：
Avram D