BACH2 drives the development and function of group 2 innate lymphoid cells

Sci Adv. 2025 Aug;11(31):eads4323. doi: 10.1126/sciadv.ads4323. Epub 2025 Aug 1.

Abstract

Group 2 innate lymphoid cells (ILC2s) represent one of the major drivers of allergic inflammation; however, the precise mechanisms governing the development and function of ILC2s remain unknown. Here, we show that the transcription factor BACH2 was abundantly expressed and epigenetically activated in ILC2s and their progenitors. Conditional ablation of BACH2 diminished the ability of ILC2 progenitors to differentiate into ILC2s. Integration of the scRNA-seq, ATAC-seq, and CUT&Tag-seq techniques revealed that BACH2 modulated the transcriptional profiles and epigenetic landscapes of ILC2 progenitors. Furthermore, BACH2 ablation compromised the functionality of ILC2s, resulting in a resolution of allergic airway inflammation. Notably, the different binding sites of BACH2 in ILC2s and TH2 cells suggested that BACH2 binds to IRF4 to control the function of ILC2, underscoring its context-specific effects on allergic airway inflammation. These findings shed promising light on the importance of BACH2 in type 2 immunity and its multifaceted role in asthma.

MeSH terms

  • Animals
  • Asthma / genetics
  • Asthma / immunology
  • Asthma / pathology
  • Basic-Leucine Zipper Transcription Factors* / genetics
  • Basic-Leucine Zipper Transcription Factors* / metabolism
  • Cell Differentiation
  • Epigenesis, Genetic
  • Immunity, Innate*
  • Interferon Regulatory Factor-4
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Lymphocytes* / cytology
  • Lymphocytes* / immunology
  • Lymphocytes* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Interferon Regulatory Factors
  • Interferon Regulatory Factor-4
  • Bach2 protein, mouse