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Updated: Nov 18, 2025

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs
Bryan C Nikolai1,2, Prashi Jain3,4, David L Cardenas3,4
1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. nikolai@bcm.edu.
Abstract:
A subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide variety of cell types. Src-3 knockout mice display broad lymphoproliferation and hypersensitivity to systemic inflammation. Using publicly available bioinformatics data and directed cellular approaches, we show that SRC-3 also is highly enriched in Tregs in mice and humans. Human Tregs lose phenotypic characteristics when SRC-3 is depleted or pharmacologically inhibited, including failure of induction from resting T cells and loss of the ability to suppress proliferation of stimulated T cells. These data support a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.
Insights
Regulatory T cells (Tregs) are crucial for preventing autoimmunity. This study reveals that the SRC-3 coactivator is essential for Treg function, highlighting its role in immune regulation and cancer evasion.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Regulatory T cells (Tregs) are vital for maintaining self-tolerance and preventing autoimmune diseases.
- The SRC-3 coactivator is implicated as an oncogene in various cancers and influences multiple transcription factors.
- SRC-3 knockout mice exhibit lymphoproliferation and heightened inflammatory responses.
Purpose of the Study:
- To investigate the role and enrichment of SRC-3 in regulatory T cells (Tregs).
- To determine the impact of SRC-3 depletion or inhibition on Treg function and characteristics.
Main Methods:
- Bioinformatic analysis of publicly available data.
- Cellular assays involving Treg induction and suppression of T cell proliferation.
- Pharmacological inhibition of SRC-3 activity.
Main Results:
- SRC-3 is significantly enriched in both mouse and human Tregs.
- Depletion or inhibition of SRC-3 impairs Treg phenotypic characteristics.
- SRC-3 deficiency leads to a loss of Treg-mediated suppression of T cell proliferation.
Conclusions:
- SRC-3 acts as a crucial coactivator in Tregs, actively contributing to the prevention of autoimmunity.
- SRC-3's role in Treg biology may facilitate immune evasion strategies employed by cancers.
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