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

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

PROVIDER: PRJNA514080 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8428440.fastq.gz	Fastqsanger.gz
	SRR8428441.fastq.gz	Fastqsanger.gz
	SRR8428442.fastq.gz	Fastqsanger.gz
	SRR8428443.fastq.gz	Fastqsanger.gz
	SRR8428444.fastq.gz	Fastqsanger.gz

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

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

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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 [Ezh2]

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

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Transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones.

Project description:Analysis of the transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones. Individual CD4+CD25High or Cd4+CD25- T cells were isolated from human PBMCs and expanded in vitro. After 3 weeks of expansion, individual clones were analysed for FOXP3 expression and in vitro suppressive activity against freshly sorted allogeneic effector T cells. This study analyses the total RNA isolated from FOXP3+ clones with suppressive potency to their non-suppressive counterparts. The resutls of this study should provide insights into the molecular pathways linking FOXP3 expression to distinct aspects of Treg phenotype and function. Total RNA obtained from individual clones of primary human regulatory and effector CD4+T cells.

2015-05-06 | E-GEOD-65650 | biostudies-arrayexpress

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

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

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Human naïve-like T follicular regulatory cells are primed for differentiation into mature Tfr and disrupted during severe infections.

Project description:Regulatory T cells (Tregs) play a pivotal role in maintaining immune self-tolerance and homeostasis. T Follicular regulatory cells (Tfr) are a specific Treg population expressing the chemokine receptor CXCR5 and is known to regulate antibody production and prevent autoantibody induction. However, the stages of Tfr formation have still not been clarified. Here we found that 30-50% of Tfr in human blood have a naïve-like phenotype (nTfr, CD45RA+CD45RO−Foxp3+CXCR5+). nTfr are expandable in vitro while retaining suppressive capacity. nTfr are transcriptionally similar to nTreg ex-vivo but after stimulation, they gain increased expression of Tfr-related suppressive molecules such as IL1RA, suggesting they are primed for full differentiation into mature Tfr. We also found that nTfr has enhanced wound healing capacity, indicating a non-canonical function of this Treg subset. Further, we demonstrate that nTfr but not nTreg are significantly reduced in the blood of COVID-19 and sepsis patients and that this loss is correlated with increased anti-Interferon-γ antibodies. Together, these data suggest that Tfr are disrupted at the earliest stage of their formation during severe disease and may be an important therapeutic target in future vaccine developments.

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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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Human naïve-like T follicular regulatory cells are primed for differentiation into mature Tfr and disrupted during severe infections. (treatment with TPC or IL2)

2025-11-14 | GSE287877 | GEO