BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection.

Xiaopeng Wu, Moujtaba Y Kasmani, Shikan Zheng, Achia Khatun, Yao Chen, Wendy Winkler, Ryan Zander, Robert Burns, Elizabeth J Taparowsky, Jie Sun, Weiguo Cui

Science immunology 2022 Jan 14

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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, we identify a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. 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. Last, 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.

Citation

Xiaopeng Wu, Moujtaba Y Kasmani, Shikan Zheng, Achia Khatun, Yao Chen, Wendy Winkler, Ryan Zander, Robert Burns, Elizabeth J Taparowsky, Jie Sun, Weiguo Cui. BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection. Science immunology. 2022 Jan 14;7(67):eabc9934