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The transcription factor Helios is critical for T regulatory cell effector differentiation in organ-specific autoimmunity [ChIP-seq]

ABSTRACT: The selective deletion of the transcription factor Helios in regulatory T cells (Tregs) leads to systemic immune activation characterized by a Th1 phenotype, hypergammaglobulinemia, and enhanced germinal center formation. We report here that these mice also exhibit acquired lipodystrophy, hepatic steatosis, and insulin resistance. A significant lymphocytic infiltrate in white adipose tissue indicated autoimmune-mediated destruction of the adipose tissue which was mediated by CD8+ T cells. In adipose tissue, Helios-deficient Tregs expressed lower levels of Tcf1/Lef1 and thus, exhibited increased effector Tregs (eTregs). However, Helios-deficient Tregs failed to generate functional terminally differentiated eTregs, including ST2+ and CXCR3+ Tregs. Helios bound to regulatory elements in multiple genes known to restrict effector generation, namely Tcf7, Lef1, Bach2, and Id3. Thus, Helios restricts eTreg generation but also enforces functional eTreg differentiation. The absence of Helios in Tregs alters eTreg generation and adipose tissue homeostasis and results in the expansion and activation of CD8+ T cells, the destruction of adipose tissue and metabolic disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE330583 | GEO | 2026/08/24

REPOSITORIES: GEO

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The transcription factor Helios is critical for T regulatory cell effector differentiation in organ-specific autoimmunity

Project description:The selective deletion of the transcription factor Helios in regulatory T cells (Tregs) leads to systemic immune activation characterized by a Th1 phenotype, hypergammaglobulinemia, and enhanced germinal center formation. We report here that these mice also exhibit acquired lipodystrophy, hepatic steatosis, and insulin resistance. A significant lymphocytic infiltrate in white adipose tissue indicated autoimmune-mediated destruction of the adipose tissue which was mediated by CD8+ T cells. In adipose tissue, Helios-deficient Tregs expressed lower levels of Tcf1/Lef1 and thus, exhibited increased effector Tregs (eTregs). However, Helios-deficient Tregs failed to generate functional terminally differentiated eTregs, including ST2+ and CXCR3+ Tregs. Helios bound to regulatory elements in multiple genes known to restrict effector generation, namely Tcf7, Lef1, Bach2, and Id3. Thus, Helios restricts eTreg generation but also enforces functional eTreg differentiation. The absence of Helios in Tregs alters eTreg generation and adipose tissue homeostasis and results in the expansion and activation of CD8+ T cells, the destruction of adipose tissue and metabolic disease.

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miR-15/16 clusters restrict effector Treg cell differentiation and function

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