Journal article
BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection
Science immunology, Vol.7(67), pp.eabc9934-eabc9934
01/01/2022
DOI: 10.1126/sciimmunol.abc9934
PMCID: PMC9005262
PMID: 35030033
Abstract
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.
Details
- Title: Subtitle
- BATF promotes group 2 innate lymphoid cell-mediated lung tissue protection during acute respiratory virus infection
- Creators
- Xiaopeng Wu - Versiti Blood Center of WisconsinMoujtaba Y. Kasmani - Versiti Blood Center of WisconsinShikan Zheng - Versiti Blood Center of WisconsinAchia Khatun - Versiti Blood Center of WisconsinYao Chen - Versiti Blood Center of WisconsinWendy Winkler - Versiti Blood Center of WisconsinRyan Zander - Versiti Blood Center of WisconsinRobert Burns - Versiti Blood Center of WisconsinElizabeth J. Taparowsky - Purdue University West LafayetteJie Sun - Mayo ClinicWeiguo Cui - Versiti Blood Center of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Science immunology, Vol.7(67), pp.eabc9934-eabc9934
- DOI
- 10.1126/sciimmunol.abc9934
- PMID
- 35030033
- PMCID
- PMC9005262
- NLM abbreviation
- Sci Immunol
- ISSN
- 2470-9468
- eISSN
- 2470-9468
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 18
- Grant note
- Cancer Research Institute Irvington Fellowship AI125741; AI148403; AI112844; AI147394; AG047156; DK127526; AI153537 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Advancing a Healthier Wisconsin Endowment (AHW) T32-GM080202 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) American Cancer Society
- Language
- English
- Date published
- 01/01/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297326702771
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