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.

Scientific Reports
|February 10, 2021
PubMed

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.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.3K
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
15.2K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.0K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

2.7K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.5K