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Differential gene expression profiling of conventional (Tconv), regulatory (Treg), follicular (TFH) helper and follicular regulatory (TFR) T-cells from control vs OX40L-Jagged-1 treated NZBWF1/j mice

ABSTRACT: Differential gene expression profiling of conventional (Tconv), regulatory (Treg), follicular (TFH) helper and follicular regulatory (TFR) T-cells from control vs OX40L-Jagged-1 treated NZBWF1/j mice

PROVIDER: PRJNA752042 | ENA |

REPOSITORIES: ENA

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Differential gene expression profiling of conventional (Tconv), regulatory (Treg), follicular (TFH) helper and follicular regulatory (TFR) T-cells from control vs OX40L-Jagged-1 treated NZBWF1/j mice

Project description:Differential gene expression profiling of conventional (Tconv), regulatory (Treg), follicular (TFH) helper and follicular regulatory (TFR) T-cells from control vs OX40L-Jagged-1 treated NZBWF1/j mice

2022-03-17 | GSE181433 | GEO

Shared and unique features distinguishing follicular T helper (TFH) and regulatory (TFR) cells from peripheral lypmh node and Peyer's Patches [Agilent-048306]

Project description:Transcriptome analyses were done comparing gene regulation of TFH and TFR cells isolated from Peyer’s Patches (PP) and immunized peripheral lymph nodes (pLN) revealing many regulatory patterns common to all follicular cells. However, in contrast to TFH cells, the kinetic but also the extent of regulation regarding many genes was attenuated in pLN TFR cells when compared to those of PP. Additionally, PP but not pLN TFR cells were largely unresponsive to IL2 and expressed Il4 as well as Il21. Together with fundamental differences in gene expression that were found between cells of both compartments this emphasizes specific adaptations of follicular T cell functions to their micro-milieu.

2018-04-16 | GSE106490 | GEO

Shared and unique features distinguishing follicular T helper (TFH) and regulatory (TFR) cells from peripheral lypmh node and Peyer's Patches [Agilent-084107]

2018-04-16 | GSE106590 | GEO

Gene expression data from OVA-immunized WT and Rptor-/- follicular regulatory T cells

Project description:Follicular regulatory T (Tfr) cells maintain homeostasis of humoral immunity by suppressing germinal center responses. TFR cells are differentiated from conventional regulatory T (Treg) cells, but underlying mechanisms remain largely unknown. We did microarray experiments to elucidate the transcriptome changes due to Rptor deficiency in Tfr cells. These data clearly demonstrate that Tfr-associated genes were down-regulated in Rptor-null Tfr cells, indicating that Raptor regulate Tfr generation by strengthening Tfr signatures.

2017-02-20 | GSE78190 | GEO

Gene expression profile of FoxP3+ CD4+ follicular regulatory T cells

Project description:Follicular regulatory T cells (TFR) are a major cellular source of negative regulation of GC antibody responses. Blimp1 is expressed by the majority of TFR cells within B cell follicles during immune responses, as well as by other tissue-specific subsets of effector Treg (eTreg). However, the potential impact of FoxP3-specific Blimp1 deletion on TFR differentiation and suppressive activity has not been evaluated. To better understand the role of Blimp1 in regulation of TFR differentiation and function, we profiled the differential gene expression in Blimp1-deficient TFR cells compared to WT control TFR cells.

2019-11-21 | GSE101611 | GEO

Follicular Regulatory T Cells Regulate the Development of Cytotoxic-like Follicular Helper T Cells

Project description:T follicular regulatory (TFR) cells are found in the germinal center (GC) response and help shape the antibody (Ab) response. Whether TFR cells have a suppressive role, a helper role or both types of roles in the GC is unclear. Here, we addressed TFR cell function using 3 different strains of TFR cell mutant mice. After immunization, GC B cells but not T follicular helper (TFH) cell positively correlated with TFR cell levels. Using a gene profiling approach, we found that TFH cells from TFR-deficient mice showed strong up-regulation of granzyme B (Gzmb) and other effector CD8 T cell genes, many of which were Stat4 dependent. This aberrant cytotoxic T cell gene profile was increased in TFR-deficient mice crossed on a pro-inflammatory background. We detected Gzmb+ and Eomesodermin+ TFH cells and a higher rate of apoptotic GC B cells in the absence of TFR cells. Klrg1+ TFH cells expressed higher Gzmb and less IL-4 and IL-21. Our data show that TFR cells repress the development of abnormal cytotoxic TFH cells that correlate with a lower GC and Ab response. This data shows a novel mode of helper function for TFR cells in the GC response.

2019-06-29 | GSE133533 | GEO

IL-12 drives the diferentiation of human T follicular regulatory cells [CUT&RUN]

Project description:T follicular regulatory (Tfr) cells can counteract the B cell-helper activity of T follicular helper (Tfh) cells and hinder the production of antibodies against self-antigens or allergens. A mechanistic understanding of the cues initiating the differentiation of T regulatory (Treg) cells into Tfr cells, which is instrumental for the therapeutic manipulation of diseases associated with a Tfr cell imbalance, is still missing. Despite their opposed roles, Tfr and Tfh cell differentiation appears to be controlled by partially overlapping signals, including TCR stimulation and costimulatory molecules. However, it is still unknown if cytokines that have been shown to control the biology of human Tfh cells, including IL-12 and activin A, can influence the differentiation of Tfr cells. To address this question, we evaluated the impact of these two cytokines on the in vitro differentiation of Tfr cells. Herein, we report a role for IL-12 and down stream Stat4 chromatin binding in driving, on activated Treg cells, the induction of molecules that belong to the Tfr cell program, including CXCR5, PD-1, BCL6 and ICOS meanwhile preserving Tfr regulatory function.

2024-04-16 | GSE252764 | GEO

IL-12 drives the diferentiation of human T follicular regulatory cells [RNA-seq]

2024-04-16 | GSE252765 | GEO

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.

2015-09-02 | E-GEOD-69756 | biostudies-arrayexpress

CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response

Project description:CD4+ follicular regulatory T cells (Tfr cells) control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development, while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we utilized a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory.

2020-11-20 | GSE161788 | GEO

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