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Updated: Jun 28, 2025

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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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

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Increased EZH2 function in regulatory T cells promotes their capacity to suppress autoimmunity by driving effector

Janneke G C Peeters, Stephanie Silveria, Merve Ozdemir

    Biorxiv : the Preprint Server for Biology
    |April 22, 2024
    PubMed

    The immunosuppressive function of regulatory T (Treg) cells is essential for maintaining immune homeostasis. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27) methyltransferase, plays a key role in maintaining Treg cell function upon CD28 co-stimulation, and Ezh2 deletion in Treg cells causes autoimmunity. Here we assessed whether increased EZH2 activity in Treg cells would improve Treg cell function. Using an Ezh2 gain-of-function mutation, Ezh2 , we found that Treg cells expressing Ezh2 displayed an increased effector Treg phenotype and were poised for improved homing to organ tissues. Expression of Ezh2 in Treg cells led to more rapid remission from autoimmunity. H3K27me3 profiling and transcriptomic analysis revealed a redistribution of H3K27me3, which prompted a gene expression profile in naïve Ezh2 Treg cells that recapitulated aspects of CD28-activated Ezh2 Treg cells. Altogether, increased EZH2 activity promotes the differentiation of effector Treg cells that can better suppress autoimmunity.

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