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- Title
Stage-specific GATA3 induction promotes ILC2 development after lineage commitment.
- Authors
Furuya, Hiroki; Toda, Yosuke; Iwata, Arifumi; Kanai, Mizuki; Kato, Kodai; Kumagai, Takashi; Kageyama, Takahiro; Tanaka, Shigeru; Fujimura, Lisa; Sakamoto, Akemi; Hatano, Masahiko; Suto, Akira; Suzuki, Kotaro; Nakajima, Hiroshi
- Abstract
Group 2 innate lymphoid cells (ILC2s) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 is a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains unclear. Herein, we identify ILC2-specific GATA3-related tandem super-enhancers (G3SE) that induce high GATA3 in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 deficiency in the bone marrow, lung, liver, and small intestine with minimal impact on other ILC lineages or Th2 cells. Single-cell RNA-sequencing and subsequent flow cytometry analysis show that GATA3 induction mechanism, which is required for entering the ILC2 stage, is lost in IL-17RB+PD-1− late ILC2-committed precursor stage in G3SE-deficient mice. Cnot6l, part of the CCR4-NOT deadenylase complex, is a possible GATA3 target during ILC2 development. Our findings implicate a stage-specific regulatory mechanism for GATA3 expression during ILC2 development. The transcription factor GATA3 is enhanced in innate lymphoid type 2 cells (ILC2). Here the authors characterize the super enhancer regions of GATA3 and show that these enhancers are required to drive GATA3 expression and stage specific ILC2 development.
- Subjects
TRANSCRIPTION factors; SUPER enhancers; TH2 cells; INNATE lymphoid cells; LUNGS; LYMPHOCYTE subsets
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49881-y