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A Gata3 enhancer necessary for ILC2 development and function.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Aug 10; Vol. 118 (32). - Publication Year :
- 2021
-
Abstract
- The type 2 helper effector program is driven by the master transcription factor GATA3 and can be expressed by subsets of both innate lymphoid cells (ILCs) and adaptive CD4 <superscript>+</superscript> T helper (Th) cells. While ILC2s and Th2 cells acquire their type 2 differentiation program under very different contexts, the distinct regulatory mechanisms governing this common program are only partially understood. Here we show that the differentiation of ILC2s, and their concomitant high level of GATA3 expression, are controlled by a Gata3 enhancer, Gata3 +674/762, that plays only a minimal role in Th2 cell differentiation. Mice lacking this enhancer exhibited defects in several but not all type 2 inflammatory responses, depending on the respective degree of ILC2 and Th2 cell involvement. Our study provides molecular insights into the different gene regulatory pathways leading to the acquisition of the GATA3-driven type 2 helper effector program in innate and adaptive lymphocytes.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Animals
Cell Differentiation genetics
Female
GATA3 Transcription Factor metabolism
Homeostasis genetics
Immunity, Innate genetics
Inflammation genetics
Inflammation physiopathology
Lymphocytes cytology
Male
Mice, Inbred C57BL
Mice, Transgenic
Strongyloidiasis parasitology
Strongyloidiasis physiopathology
Th2 Cells pathology
Th2 Cells physiology
Mice
Enhancer Elements, Genetic
GATA3 Transcription Factor genetics
Lymphocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 118
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 34353913
- Full Text :
- https://doi.org/10.1073/pnas.2106311118