Stage-specific GATA3 induction promotes ILC2 development after lineage commitment.
Nat Commun
; 15(1): 5610, 2024 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-38969652
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos
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Linaje de la Célula
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Factor de Transcripción GATA3
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Inmunidad Innata
Límite:
Animals
Idioma:
En
Año:
2024
Tipo del documento:
Article