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Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE123488 | GEO | 2019/03/18

REPOSITORIES: GEO

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Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs [ATAC-seq]

Project description:Genetic variants at the PTPN2 locus, which encodes the tyrosine phosphatase PTPN2, cause reduced gene expression and are linked to rheumatoid arthritis (RA) and other autoimmune diseases. PTPN2 inhibits signaling through the T cell and cytokine receptors and loss of PTPN2 promotes T cell expansion and CD4 and CD8-driven autoimmunity. However, it remains unknown whether loss of PTPN2 in FoxP3+ regulatory T cells (Treg) plays a role in autoimmunity. Here we show that a reduction in Ptpn2 expression, comparable to that reported in human carriers of autoimmune-predisposing PTPN2 variants, unexpectedly enhances the severity of autoimmune arthritis through a Treg-intrinsic mechanism. Mechanistically, we found that through dephosphorylation of STAT3, Ptpn2 inhibits IL-6-driven pathogenic loss of FoxP3 after Tregs have acquired RORgt expression, at a stage when chromatin accessibility for STAT3-targeted IL-17 associated transcription factors is maximized. We conclude that PTPN2 promotes FoxP3 stability in RORgt+ Treg and that loss of function of PTPN2 in Treg contributes to the association between PTPN2 and autoimmunity.

2019-03-18 | GSE123486 | GEO

Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs [RNA-seq]

2019-03-18 | GSE123484 | GEO

Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs

Project description:Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs

| PRJNA508897 | ENA

Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs [ATAC-seq]

Project description:Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs [ATAC-seq]

| PRJNA508900 | ENA

Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs [RNA-seq]

Project description:Loss-of-function of PTPN2 promotes pathogenic loss of FoxP3+ in RORgt+ Tregs [RNA-seq]

| PRJNA508898 | ENA

Reduced expression of phosphatase PTPN2 promotes pathogenic conversion of Tregs in autoimmunity.

Project description: Not available

| S-EPMC6391091 | biostudies-literature

Foxp3 promotes macrophage phagocytosis in AIS

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-31 | GSE206946 | GEO

Eomes regulates mitochondrial function and promotes survival of pathogenic CD4+ T cells during chronic inflammation

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-23 | GSE247863 | GEO

Foxp3+RORgt+ TCR Sequencing

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Loss of the repressor REST affects progesterone receptor function and promotes uterine leiomyoma pathogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

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