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Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen Treg and Tconv RbpjWT expression]

ABSTRACT: Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen Treg and Tconv RbpjWT expression]

PROVIDER: PRJNA488286 | ENA |

REPOSITORIES: ENA

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Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen Treg and Tconv RbpjWT expression]

Project description:The transcriptional regulator Rbpj is involved in T-helper (TH) subset polarization, but its function in Treg cells remains unclear. Here we show that Treg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of Treg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient Treg cells in controlling TH2 polarization and B cell responses was observed, leading to the spontaneous formation of germinal centers and a TH2-associated immunoglobulin class switch as well as T-cell polarization into TH2 effector cells. The observed phenotype was environment-dependent and could be induced by infection with parasitic nematodes. Rbpj-deficient Treg cells adopted open chromatin landscapes and gene expression profiles reminiscent of tissue-derived TH2-polarized Treg cells, with a prevailing footprint of transcription factor Gata-3. The over-expression of Ilt3 rendered Rbpj-deficient Treg cells incompatible to specifically restrain TH2 responses, finally leading to severe and fatal lymphoproliferative disease.

2019-01-31 | GSE119162 | GEO

Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen Treg and Tconv RbpjKO expression]

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Rbpj expression in regulatory T cells is critical for restraining TH2 responses [affected and unaffected spleen Treg and Tconv RbpjKO and RbpjWT expression]

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Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen Rbpj WT and Rbpj KO ATAC-seq]

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Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen RbpjKO sick expression]

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Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen RbpjKO and RbpjWT RNA-seq]

Project description:The transcriptional regulator Rbpj is involved in T-helper (TH) subset polarization, but its function in Treg cells remains unclear. Here we show that Treg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of Treg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient Treg cells in controlling TH2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a TH2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient Treg cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived TH2-polarized Treg cells, with a prevailing footprint of the transcription factor Gata-3. Taken together, our study suggest that Treg cells require Rbpj to specifically restrain TH2 responses, including their own excessive TH2-like differentiation potential.

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