Autoimmunity induced by epigenome alteration affecting thymic Treg cell development.

MBD3 deficiency in T cells causes multiorgan autoimmune disease by reducing thymic Treg cell development, notably decreasing CD25+ Foxp3+ Treg cells in mice.

• Why it matters: Understanding how epigenetic alterations affect Treg cell development is crucial because Tregs maintain immune tolerance, and their deficiency can lead to autoimmunity.
• What they did: The study used MBD3-deficient mice and mixed bone marrow chimeras to analyze thymic Treg cell differentiation, focusing on transcriptional and functional impacts on Treg-specific gene enhancers.
• The result: MBD3 deficiency impairs activation of the Il2ra enhancer, reducing CD25 expression in thymic immature CD4 single-positive thymocytes, limiting Treg precursor generation and thymic Treg output, which may explain autoimmune development.