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Updated: Oct 25, 2025

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A Gata3 enhancer necessary for ILC2 development and function.

Darshan N Kasal1,2, Zhitao Liang1,2, Maile K Hollinger1,3

  • 1Committee on Immunology, University of Chicago, Chicago, IL 60637.

Proceedings of the National Academy of Sciences of the United States of America
|August 6, 2021
PubMed
Summary
This summary is machine-generated.

A specific GATA3 enhancer drives type 2 helper cell differentiation in innate lymphoid cells (ILCs) but not adaptive T helper (Th) cells. This finding reveals distinct regulatory pathways for common immune effector programs.

Keywords:
GATA3ILC2Th2 cellinnate lymphoid celltype 2 immunity

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The type 2 helper effector program is regulated by the transcription factor GATA3.
  • Both innate lymphoid cells (ILCs) and adaptive CD4+ T helper (Th) cells express this program.
  • The distinct regulatory mechanisms governing this common program are not fully understood.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling GATA3 expression and type 2 helper cell differentiation in ILCs and Th2 cells.
  • To identify specific genetic elements that differentially regulate GATA3 in innate versus adaptive type 2 helper cells.

Main Methods:

  • Utilized a mouse model lacking the *Gata3* +674/762 enhancer.
  • Assessed type 2 inflammatory responses in knockout mice.
  • Analyzed the differentiation and GATA3 expression levels in ILC2s and Th2 cells.

Main Results:

  • The *Gata3* +674/762 enhancer is crucial for ILC2 differentiation and high GATA3 expression.
  • This enhancer plays a minimal role in Th2 cell differentiation.
  • Mice lacking the enhancer showed impaired, but not abolished, type 2 inflammatory responses, with varying impact based on ILC2 and Th2 cell contribution.

Conclusions:

  • The *Gata3* +674/762 enhancer differentially regulates GATA3-driven type 2 effector programs in innate and adaptive lymphocytes.
  • This study provides molecular insights into the distinct gene regulatory pathways governing type 2 immunity in ILCs and Th cells.