Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE87399 | GEO | 2017/12/01
SECONDARY ACCESSION(S): PRJNA344662
REPOSITORIES: GEO
Similar Datasets
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
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.
2015-09-02 | GSE69756 | GEO
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
Project description:Peanut-specific IgE is present with peanut sensitizations at day 1 an day 8, while is absent with peanut sensitizations at day 1 and day 3. Since TFH and TFR cells are import in regulating antibody response in germinal center, we would like to know the different in TFH and TFR cells between D1D3 and D1D8 peanut sensitizations.
2022-06-28 | GSE202713 | GEO
Project description:Tfh and B cells were cultured together with or without Tfr cells. After 4 days Tfh and B cells were sorted and prepared for 3' targeted RNA-seq.
2016-10-02 | GSE81999 | GEO
Project description:By using RNA-sequencing assay on sorted Sostdc1-EGFP- Tfh, Sostdc1+ Tfh and Non-Tfh cells and single cell RNA-seq assay on sorted CD4+CD44+T cells from Sostdc1-EGFP reporter mice, support the conclusion that Sostdc1+ Tfh cells are a distinct subpopulation of Tfh cells.After performing the RNA-seq assessment and ATAC-seq on Tfr and Treg cells from WT and Sostdc1 KO mice,demonstrated that Sostdc1 ablation predominantly augmented β-catenin-controlled transcriptome, which in turn resulted in Tfr cell failure.
2020-08-21 | GSE142523 | GEO
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 | GSE106590 | GEO
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
Project description:Leber2016 - Expanded model of Tfh-Tfr
differentiation - Helicobacter pylori infection
The parameters used in the model were
obtained from experiments conducted by the authors, previous
publications [
1,
2,
3] and
parameter optimisation carried out in the paper using particle
swarm and genetic algorithms.
This model is described in the article:
Bistability analyses of CD4+
T follicular helper and regulatory cells during Helicobacter
pylori infection.
Leber A, Abedi V, Hontecillas R,
Viladomiu M, Hoops S, Ciupe S, Caughman J, Andrew T,
Bassaganya-Riera J.
J. Theor. Biol. 2016 Jun; 398:
74-84
Abstract:
T follicular helper (Tfh) cells are a highly plastic subset
of CD4+ T cells specialized in providing B cell help and
promoting inflammatory and effector responses during infectious
and immune-mediate diseases. Helicobacter pylori is the
dominant member of the gastric microbiota and exerts both
beneficial and harmful effects on the host. Chronic
inflammation in the context of H. pylori has been linked to an
upregulation in T helper (Th)1 and Th17 CD4+ T cell phenotypes,
controlled in part by the cytokine, interleukin-21. This study
investigates the differentiation and regulation of Tfh cells,
major producers of IL-21, in the immune response to H. pylori
challenge. To better understand the conditions influencing the
promotion and inhibition of a chronically elevated Tfh
population, we used top-down and bottom-up approaches to
develop computational models of Tfh and T follicular regulatory
(Tfr) cell differentiation. Stability analysis was used to
characterize the presence of two bi-stable steady states in the
calibrated Tfh/Tfr models. Stochastic simulation was used to
illustrate the ability of the parameter set to dictate two
distinct behavioral patterns. Furthermore, sensitivity analysis
helped identify the importance of various parameters on the
establishment of Tfh and Tfr cell populations. The core network
model was expanded into a more comprehensive and predictive
model by including cytokine production and signaling pathways.
From the expanded network, the interaction between TGFB-Induced
Factor Homeobox 1 (Tgif1) and the retinoid X receptor (RXR) was
displayed to exert control over the determination of the Tfh
response. Model simulations predict that Tgif1 and RXR
respectively induce and curtail Tfh responses. This
computational hypothesis was validated experimentally by
assaying Tgif1, RXR and Tfh in stomachs of mice infected with
H. pylori.
The impulse of RXR as shown in the paper
(figure 7C) can be implemented by creating an event in the curated
SBML file.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000625.
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2015-05-25 | BIOMD0000000625 | BioModels
Project description:Tissue Specific Transcriptional Profiling of Tfh, Tfr, Treg and Tcon
2019-01-25 | GSE124883 | GEO