| RRC ID |
88556
|
| 著者 |
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.
|
| タイトル |
Stage-specific GATA3 induction promotes ILC2 development after lineage commitment.
|
| ジャーナル |
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.
|
| 巻・号 |
15(1)
|
| ページ |
5610
|
| 公開日 |
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
|
| リソース情報 |
| 実験動物マウス |
RBRC00144 |
