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Chromatin accessibility landscapes of WT (GFP-) and BATF KO (GFP+) ILC3s sorted from lung mature ILC2s

ABSTRACT: Activated type 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 identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE188275 | GEO | 2022/01/14

REPOSITORIES: GEO

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Characterization of lung innate lymphoid cells during influenza infection using scRNA-seq

Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, whether an ILC2 subset that specializes in wound healing exists, and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played 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.

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Chromatin accessibility landscapes of WT and Batf-/- ILC2s sorted from lungs at day 9 after influenza virus infection

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