RRC ID 88556
Author Furuya H, Toda Y, Iwata A, Kanai M, Kato K, Kumagai T, Kageyama T, Tanaka S, Fujimura L, Sakamoto A, Hatano M, Suto A, Suzuki K, Nakajima H.
Title Stage-specific GATA3 induction promotes ILC2 development after lineage commitment.
Journal Nat Commun
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.
Volume 15(1)
Pages 5610
Published 2024-7-5
DOI 10.1038/s41467-024-49881-y
PII 10.1038/s41467-024-49881-y
PMID 38969652
PMC PMC11226602
MeSH Animals Cell Differentiation / immunology Cell Lineage* Enhancer Elements, Genetic / genetics GATA3 Transcription Factor* / genetics GATA3 Transcription Factor* / metabolism Immunity, Innate* Lymphocytes* / cytology Lymphocytes* / immunology Lymphocytes* / metabolism Mice Mice, Inbred C57BL Mice, Knockout Single-Cell Analysis Th2 Cells / immunology
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Mice RBRC00144