Epigenetic signature induced by prolonged culture may impact therapeutic function of Tregs used in adoptive cell therapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA771074 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Adoptive transfer of regulatory T cells (Treg) is a promising new therapeutic option to treat detrimental inflammatory conditions. To reach sufficient cell yield for treatment, ex vivo isolated autologous or allogenic Tregs need to be expanded extensively in vitro during manufacturing of the Treg product. However, repetitive cycles of restimulation and prolonged culture have been shown to impact T cell phenotypes, functionality and fitness. We performed genome-wide DNA methylation profiling of cells throughout the manufacturing process of a polyclonal Treg product, which may be informative for predicting the cellular state and function of the final Treg product.
2021-10-15 | GSE185854 | GEO
Project description:We isolated visceral adipose tissue (VAT) Tregs from Foxp3.YFP-Cre Bmal1WT or Foxp3.YFP-Cre bmal1flox mice fed a normal lean diet or a high-fat diet. VAT Tregs were also sorted after adoptive transfer. We found that Bmal1KO Tregs are more activated in lean mice, after 4 weeks HFD and after adoptive transfer, but loseVAT Treg signature after 16 weeks of high-fat diet feeding.
2022-07-28 | GSE206775 | GEO
Project description:Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine. FACS purified Foxp3+ Tregs were stimulated in the presence of media or IL-27 to compare IL-27 induced gene profiles. Four samples (media stimulated or IL-27-stimulated) were collected from four independent experiments. Genes altered by IL-27 treatment were compared to those of media stimulated Tregs.
2015-11-01 | E-GEOD-63455 | biostudies-arrayexpress
Project description:Transcriptome analysis of naïve Tregs, memory Tregs and CD161+ Tregs
| PRJNA489005 | ENA
Project description:The aim of the project is to do proteomic analysis of total cell lysate from rest and activated mouse Tregs. The proteomic data were mapped to the Gene Ontology Cellular Component (GOCC)database to obtain the list of membrane proteins on activated Tregs. The set of membrane proteins identified were compared with the potential Siglec-1 counter-receptors on activated Tregs.
2021-04-28 | PXD022259 | Pride
Project description:ATAC-seq data from naïve Tregs, memory Tregs and CD161+ Tregs
| PRJNA489004 | ENA
Project description:To characterize Brg1-reexpressed Tregs, we treated 3-wks-old rKO1 mice with the low dose of TAM and compared gene expression patterns in Brg1-deleted (GFP+) vs. Brg1-reexpressed (GFP- ) Treg subsets isolated 7 days after TAM. Brg1-deletion in the mosaic females and Brg1-reexpression in rKO1 mice on Day 7 after TAM treatment affected 618 and 1352 genes, respectively, with only 241 genes shared, suggesting divergent roles of Brg1 under the physiological vs. inflammatory conditions. These genes can be divided into two categories: the “naïve genes” that are predominantly expressed in naïve Tregs and “activation/effector function genes” preferentially expressed in activated/effector Tregs. Our data collectively suggest that Brg1 reexpression acted (partly) in conjunction with inflammatory cytokines to convert Brg1-deleted Tregs into hyperactivated Tregs endowed with potent suppressive activity
2020-02-21 | GSE132562 | GEO
Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses. TIGIT+ and TIGIT- Tregs were sorted from naïve Foxp3-GFP KI mice (pooled spleen and lymph nodes) TIGIT: T cell immunoreceptor with Ig and ITIM domains
2014-12-12 | E-GEOD-56299 | biostudies-arrayexpress
Project description:Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine.
2015-11-01 | GSE63455 | GEO
Project description:The objective of this study was to determine if a subset of regulatory T cells (Tregs) expressing the transcription factor, Zbtb20, played a unique role in the function of the immune system. Genetic reporter mice were used to isolate Zbtb20-expressing Tregs as well as activated (CD62Llo) and naive (CD62Lhi) Tregs. The gene expression in these cells was determined with RNA-seq.
2022-02-25 | E-MTAB-11442 | biostudies-arrayexpress