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Updated: Sep 8, 2025

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
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Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

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Steroid nuclear receptor coactivator 2 controls immune tolerance by promoting induced Treg differentiation via

Wencan Zhang1, Xu Cao2, Xiancai Zhong1

  • 1Department of Immunology and Theranostics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.

Science Advances
|June 15, 2022
PubMed

Insights

Steroid nuclear receptor coactivator 2 (SRC2) promotes regulatory T cell (Treg) differentiation, unlike SRC1. Mice lacking SRC2 in Tregs develop autoimmunity, highlighting SRC2

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Steroid nuclear receptor coactivator 1 (SRC1) inhibits regulatory T cell (Treg) differentiation.
  • SRC2 is a member of the SRC family of transcription coactivators.
  • Tregs are crucial for immune tolerance.

Purpose of the Study:

  • To investigate the role of SRC2 in Treg differentiation and immune tolerance.
  • To determine the mechanism by which SRC2 influences Treg development.
  • To explore the therapeutic potential of SRC family coactivators.

Main Methods:

  • Generating mice deficient for SRC2 specifically in Tregs.
  • Analyzing Treg differentiation in wild-type and SRC2-deficient mice.
  • Assessing autoimmune phenotypes in aged SRC2-deficient mice.
  • Investigating the molecular mechanism involving NFAT1, Nr4a2, and Foxp3.

Main Results:

  • SRC2 stimulates Treg differentiation, contrasting with SRC1's inhibitory role.
  • SRC2 is not essential for thymic Treg development but is critical for naive CD4+ T cell Treg differentiation.
  • SRC2-deficient mice exhibit spontaneous autoimmune phenotypes, including splenomegaly and lung inflammation.
  • SRC2-deficient mice show exacerbated experimental autoimmune encephalomyelitis (EAE) due to reduced Tregs.
  • Mechanistically, SRC2, via NFAT1, activates Nr4a2 expression, promoting Foxp3 and Treg differentiation.

Conclusions:

  • SRC2 plays a distinct and crucial role in promoting Treg differentiation.
  • Dysregulation of SRC2 contributes to autoimmune diseases.
  • SRC family coactivators have differential roles in Treg biology and represent potential therapeutic targets for immune tolerance modulation.

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