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FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [tissue]

ABSTRACT: Tissue Specific Transcriptional Profiling of Tfh, Tfr, Treg and Tcon

ORGANISM(S): Mus musculus

PROVIDER: GSE124883 | GEO | 2019/01/25

REPOSITORIES: GEO

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FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [Ezh2]

Project description:Tfr cells from Ezh2 floxed FoxP3 Cre mice

2019-01-25 | GSE124881 | GEO

FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [InVitro Ex-Tfr]

Project description:InVitro Ex-Tfr RNAseq

2019-01-25 | GSE124882 | GEO

FoxP3 and Ezh2 regulate Tfr cell suppressive function and transcriptional program.

Project description:Follicular regulatory T (Tfr) cells are a regulatory T cell subset that controls antibody production by inhibiting T follicular helper (Tfh)-mediated help to B cells. Tfh and Tfr cells possess opposing functions suggesting unique programming. Here we elucidated the transcriptional program controlling Tfr suppressive function. We found that Tfr cells have a program for suppressive function fine-tuned by tissue microenvironment. The transcription factor FoxP3 and chromatin-modifying enzyme EZH2 are essential for this transcriptional program but regulate the program in distinct ways. FoxP3 modifies the Tfh program to induce a Tfr-like functional state, demonstrating that Tfr cells coopt the Tfh program for suppression. Importantly, we identified a Tfr cell population that loses the Tfr program to become "ex-Tfr" cells with altered functionality. These dysfunctional ex-Tfr cells may have roles in modulating pathogenic antibody responses. Taken together, our studies reveal mechanisms controlling the Tfr transcriptional program and how failure of these mechanisms leads to dysfunctional Tfr cells.

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Decreased TFR/TFH ratio in SIV-infected rhesus macaques may contribute to accumulation of TFH cells in chronic infection

Project description:T follicular helper cells (TFH) are critical for the development and maintenance of germinal centers (GC) and humoral immune responses. During chronic HIV/SIV infection TFH accumulate, possibly as a result of antigen persistence. The HIV/SIV-associated TFH expansion may also reflect lack of regulation by suppressive follicular regulatory CD4+ T-cells (TFR). TFR are natural regulatory T-cells (TREG) that migrate into the follicle and, similarly to TFH, up-regulate CXCR5, Bcl-6, and PD1. Here we identified TFR as CD4+CD25+FoxP3+CXCR5+PD1hiBcl-6+ within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry. RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FoxP3, Bcl-6, PRDM1, IL-10, and IL-21. In healthy, SIV-uninfected RM, we observed a negative correlation between frequencies of TFR and both TFH and GC B-cells as well as levels of CD4+ T-cell proliferation. Following SIV infection, the TFR/TFH ratio was reduced with no change in the frequency of TREG or TFR within the total CD4+ T-cell pool. Finally, we examined whether higher levels of direct virus infection of TFR were responsible for their relative depletion post-SIV infection. We found that TFH, TFR and TREG sorted from SIV- infected RM harbor comparable levels of cell-associated viral DNA. Our data suggests that TFR may contribute to the regulation and proliferation of TFH and GC B-cells in vivo and that a decreased TFR/TFH ratio in chronic SIV infection may lead to unchecked expansion of both TFH and GC B-cells. TFR, TFH, TREG and bulk CD4 cells were sorted from spleens of 5 uninfected and 5 infected RM.

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FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [InVitro Ex-Tfr]

Project description:FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [InVitro Ex-Tfr]

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scRNA-seq of human Tfh, Tfr and Treg cells sorted from Tonsil, Iliac Lymph Node and PBMCs

Project description:The datasets were obtained to investigate the transcriptional profile of Tfh, Tfr and Treg cells isolated from different human tissues. The comparison between lymphoid tissues with different frequency of the most mature Tfh and Tfr cells allows the investigation of maturation as well as tissue adaptation of those different cell subsets. To address these issues, three different cell populations from three different tissues were sorted by index sorting, with Tfh cells as CD4+CXCR5+ICOS+; Tfr cells as CD4+CXCR5+CD25+ and Treg cells as CD4+CXCR5-CD25+. Smart-seq2 protocol was used mRNA library preparations.

2021-04-22 | E-MTAB-10364 | biostudies-arrayexpress

FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [Ezh2]

Project description:FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [Ezh2]

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Project description:FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program

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FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [tissue]

Project description:FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program [tissue]

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FoxP3 and Ezh2 Regulate Tfr cell Suppressive Function and Transcriptional Program

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