T cell-intrinsic cGAS-CTCF regulation maintains regulatory T cell development and function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1287524 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:T cell-intrinsic cGAS-CTCF regulation maintains regulatory T cell development and function [CTCF-CR]
| PRJNA1285936 | ENA
Project description:Cyclic GMP-AMP synthase (cGAS) is a cytosolic double-strand DNA (dsDNA) sensor in innate immune cells. A function of cGAS is to detect cytosolic double-stranded DNA and synthesize the cyclic dinucleotide 2'3'-cGAMP. This second messenger binds to and activates the adaptor protein STING, triggering the TBK1-IRF3 signaling pathway. However, the function of cGAS in T cells remain unknown and its role in adaptive immunity is also poorly characterized. Here we show that nuclear cGAS promotes regulatory T cell (Treg) development by cooperating with the genome organizer CTCF through a T cell-intrinsic and synthase function-independent way. Conditional deletion of cGAS using Foxp3Cre-YFP Cgasfl/fl and CD4Cre Cgasfl/fl mice demonstrated that cGAS imprints thymocytes for Treg development before the expression of FOXP3. cGAS also promotes the FOXP3 inheritability and suppressive activity of Treg. At steady state, cGAS is located in the nucleus of Treg, while stimulation of naïve CD4+ T cell with anti-CD3/CD28 antibodies induces transcription of cGAS and its translocation into nucleus. ATAC-sequencing of thymic Treg and Treg precursors revealed that CTCF binding is reduced in mature Treg. Mechanistically, cGAS interacts with CTCF and recruits CTCF to Tnfrsf9 (4-1BB) and Tnfrsf4 (OX40) gene locus to maintain their stable transcription through formation of chromatin loops. Physiologically, in mouse tumor model, Treg specific deletion of cGAS reduced tumor growth. Therefore, we uncovered a T cell-intrinsic role of nuclear cGAS in maintaining Treg development and function by imprinting the genome architecture with CTCF.
2025-08-07 | GSE301662 | GEO
Project description:Cyclic GMP-AMP synthase (cGAS) is a cytosolic double-strand DNA (dsDNA) sensor in innate immune cells. A function of cGAS is to detect cytosolic double-stranded DNA and synthesize the cyclic dinucleotide 2'3'-cGAMP. This second messenger binds to and activates the adaptor protein STING, triggering the TBK1-IRF3 signaling pathway. However, the function of cGAS in T cells remain unknown and its role in adaptive immunity is also poorly characterized. Here we show that nuclear cGAS promotes regulatory T cell (Treg) development by cooperating with the genome organizer CTCF through a T cell-intrinsic and synthase function-independent way. Conditional deletion of cGAS using Foxp3Cre-YFP Cgasfl/fl and CD4Cre Cgasfl/fl mice demonstrated that cGAS imprints thymocytes for Treg development before the expression of FOXP3. cGAS also promotes the FOXP3 inheritability and suppressive activity of Treg. At steady state, cGAS is located in the nucleus of Treg, while stimulation of naïve CD4+ T cell with anti-CD3/CD28 antibodies induces transcription of cGAS and its translocation into nucleus. ATAC-sequencing of thymic Treg and Treg precursors revealed that CTCF binding is reduced in mature Treg. Mechanistically, cGAS interacts with CTCF and recruits CTCF to Tnfrsf9 (4-1BB) and Tnfrsf4 (OX40) gene locus to maintain their stable transcription through formation of chromatin loops. Physiologically, in mouse tumor model, Treg specific deletion of cGAS reduced tumor growth. Therefore, we uncovered a T cell-intrinsic role of nuclear cGAS in maintaining Treg development and function by imprinting the genome architecture with CTCF.
2025-08-07 | GSE301661 | GEO
Project description:Cyclic GMP-AMP synthase (cGAS) is a cytosolic double-strand DNA (dsDNA) sensor in innate immune cells. A function of cGAS is to detect cytosolic double-stranded DNA and synthesize the cyclic dinucleotide 2'3'-cGAMP. This second messenger binds to and activates the adaptor protein STING, triggering the TBK1-IRF3 signaling pathway. However, the function of cGAS in T cells remain unknown and its role in adaptive immunity is also poorly characterized. Here we show that nuclear cGAS promotes regulatory T cell (Treg) development by cooperating with the genome organizer CTCF through a T cell-intrinsic and synthase function-independent way. Conditional deletion of cGAS using Foxp3Cre-YFP Cgasfl/fl and CD4Cre Cgasfl/fl mice demonstrated that cGAS imprints thymocytes for Treg development before the expression of FOXP3. cGAS also promotes the FOXP3 inheritability and suppressive activity of Treg. At steady state, cGAS is located in the nucleus of Treg, while stimulation of naïve CD4+ T cell with anti-CD3/CD28 antibodies induces transcription of cGAS and its translocation into nucleus. ATAC-sequencing of thymic Treg and Treg precursors revealed that CTCF binding is reduced in mature Treg. Mechanistically, cGAS interacts with CTCF and recruits CTCF to Tnfrsf9 (4-1BB) and Tnfrsf4 (OX40) gene locus to maintain their stable transcription through formation of chromatin loops. Physiologically, in mouse tumor model, Treg specific deletion of cGAS reduced tumor growth. Therefore, we uncovered a T cell-intrinsic role of nuclear cGAS in maintaining Treg development and function by imprinting the genome architecture with CTCF.
2025-08-07 | GSE301664 | GEO
Project description:Cyclic GMP-AMP synthase (cGAS) is a cytosolic double-strand DNA (dsDNA) sensor in innate immune cells. A function of cGAS is to detect cytosolic double-stranded DNA and synthesize the cyclic dinucleotide 2'3'-cGAMP. This second messenger binds to and activates the adaptor protein STING, triggering the TBK1-IRF3 signaling pathway. However, the function of cGAS in T cells remain unknown and its role in adaptive immunity is also poorly characterized. Here we show that nuclear cGAS promotes regulatory T cell (Treg) development by cooperating with the genome organizer CTCF through a T cell-intrinsic and synthase function-independent way. Conditional deletion of cGAS using Foxp3Cre-YFP Cgasfl/fl and CD4Cre Cgasfl/fl mice demonstrated that cGAS imprints thymocytes for Treg development before the expression of FOXP3. cGAS also promotes the FOXP3 inheritability and suppressive activity of Treg. At steady state, cGAS is located in the nucleus of Treg, while stimulation of naïve CD4+ T cell with anti-CD3/CD28 antibodies induces transcription of cGAS and its translocation into nucleus. ATAC-sequencing of thymic Treg and Treg precursors revealed that CTCF binding is reduced in mature Treg. Mechanistically, cGAS interacts with CTCF and recruits CTCF to Tnfrsf9 (4-1BB) and Tnfrsf4 (OX40) gene locus to maintain their stable transcription through formation of chromatin loops. Physiologically, in mouse tumor model, Treg specific deletion of cGAS reduced tumor growth. Therefore, we uncovered a T cell-intrinsic role of nuclear cGAS in maintaining Treg development and function by imprinting the genome architecture with CTCF.
2025-08-07 | GSE301663 | GEO
Project description:T cell-intrinsic cGAS-CTCF regulation maintains regulatory T cell development and function [Hi-C]
| PRJNA1285937 | ENA
Project description:T cell-intrinsic cGAS-CTCF regulation maintains regulatory T cell development and function [scRNA-Seq]
| PRJNA1285940 | ENA
Project description:T cell-intrinsic cGAS-CTCF regulation maintains regulatory T cell development and function [ATAC-seq]
| PRJNA1285939 | ENA
Project description:cGAS maintains basal antiviral state
| PRJNA839440 | ENA
Project description:Upon recognition of aberrantly located DNA, the innate immune sensor cGAS activates STING/IRF-3-driven antiviral responses. Here we characterized the ability of a specific variant of the cGAS-encoding gene MB21D1, rs610913, to alter cGAS-mediated DNA sensing and viral infection. rs610913 is a frequent G>T polymorphism resulting in a P261H exchange in the cGAS protein. Data from the International Collaboration for the Genomics of HIV suggested that rs610913 nominally associates with HIV-1 acquisition in vivo. Molecular modeling of cGAS(P261H) hinted towards the possibility for an additional binding site for a potential cellular co-factor in cGAS dimers. However, cGAS(WT) or cGAS(P261H)-reconstituted THP-1 cGAS KO cells shared steady-state expression of interferon-stimulated genes (ISGs), as opposed to cells expressing the enzymatically inactive cGAS(G212A/S213A). Accordingly, cGAS(WT) and cGAS(P261H) cells were less susceptible to lentiviral transduction and infection with HIV-1, HSV-1, and Chikungunya virus as compared to cGAS KO- or cGAS(G212A/S213A) cells. Upon DNA challenge, innate immune activation appeared to be mildly reduced upon expression of cGAS(P261H) compared to cGAS(WT). Finally, DNA challenge of PBMCs from donors homozygously expressing rs610913 provoked a trend towards a slightly reduced type I IFN response as compared to PBMCs from GG donors. Taken together, the steady-state activity of cGAS maintains a base-line antiviral state rendering cells more refractory to ISG-sensitive viral infections. rs610913 failed to grossly differ phenotypically from the wild-type gene, suggesting that cGAS(P261H) and wild-type cGAS share a similar ability to sense viral infections in vivo.
2022-05-25 | GSE203334 | GEO