The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells [seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE67960 | GEO | 2015/04/29
SECONDARY ACCESSION(S): PRJNA281380
REPOSITORIES: GEO
Similar Datasets
Project description:Using an unbiased chemical biology approach, we discover harmine as a novel regulator of Treg/Th17 differentiation. Harmine enhances Treg differentiation (working in conjunction with low levels of exogenous TGFb) and inhibits Th17 differentiation. Analysis of global gene expression of Tregs generated using low TGFb + harmine reveals significant similarity to Tregs generated using high TGFb only and suggests relevance of harmine-engaged mechanisms to IBD. Naïve CD4+CD62L+ T cells were purified from Foxp3GFP mice either by MACS or FACS, then cultured in either low TGFb + harmine or high TGFb conditions. GFP+ Tregs were sorted by FACS at day 4.
2015-04-29 | E-GEOD-64247 | biostudies-arrayexpress
Project description:Using an unbiased chemical biology approach, we discover harmine as a novel regulator of Treg/Th17 differentiation. Harmine enhances Treg differentiation (working in conjunction with low levels of exogenous TGFb) and inhibits Th17 differentiation. Analysis of global gene expression of Tregs generated using low TGFb + harmine reveals significant similarity to Tregs generated using high TGFb only and suggests relevance of harmine-engaged mechanisms to IBD.
2015-04-29 | GSE64247 | GEO
Project description:Tcf1, the DNA-binding partner of β-catenin, is essential for the development and function of T regulatory cells (Tregs). However, how Tcf1 regulates Treg functional specification is less understood. Here, we ablated Tcf1 in Tregs to elucidate its role in Treg specification in healthy mice and mice with colon cancer. RNAseq and single-cell RNAseq revealed that Tcf1 deficient Tregs maintain their core transcriptional signature and diversity, but promote T-cell receptor, Tgfβ receptor, TH17, and Wnt/β-catenin signaling pathways. Central-memory-Tregs with low Klf2 and effector-Tregs with high Mif expression gain TH17 characteristics and mature into effector Treg subpopulations that strongly express cMaf. Tcf1 deficient Tregs exhibit enhanced suppression of T-cell proliferation and cytotoxicity but are compromised in controlling CD4+ T-cell polarization and inflammation. In mice with polyposis, Tcf1 deficient Tregs promote inflammation and tumor growth. Thus, Tcf1 determines Treg functions that regulate TH17 inflammation and the course and outcome of colorectal cancer.
2021-06-01 | GSE163084 | GEO
Project description:Regulatory T cells (Tregs) inhibit effector T cells and maintain immune system homeostasis. Treg maturation in peripheral sites (pTregs) is poorly understood but is known to require inhibition of protein kinase mTORC1 (e.g.RAD001) and exposure to TGFb. Paradoxically, Treg maturation requires protein synthesis yet mTORC1 inhibition downregulates it, leaving unanswered how Tregs carry-out essential mRNA translation for development and immune suppression activity. Using human CD4+ T cells differentiated in culture (iTregs) and genome-wide transcription and translation profiling, we show that TGFb transcriptionally reprograms naïve T cells to express iTreg differentiation and immune suppression mRNAs, while mTORC1 inhibition impairs translation of T cell mRNAs but not those induced by TGFb. TGFb-induced Treg mRNAs were found to utilize an alternate mechanism for cap-dependent mRNA translation directed by the DAP5/eIF3d complex rather than canonical mTORC1/eIF4E during Treg development, which is directed by their 5’-untranslated regions. iTreg differentiation is therefore mediated by combined TGFb transcriptional and translational reprogramming and a privileged mechanism of mRNA translation
2021-06-22 | GSE178634 | GEO
Project description:The therapeutic use of regulatory T cells (Tregs) in patients with autoimmune disorders has been hampered by the biological variability of memory Treg populations in the peripheral blood. In this study, we reveal through a combination of quantitative proteomic, multiparametric flow cytometry, RNA-seq data analysis and functional assays, that CD49f is heterogeneously expressed among human Tregs and impacts their immunomodulatory function. High expression of CD49f defines a subset of dysfunctional Tregs in the human blood characterized by a Th17-like phenotype and impaired suppressive capacity. CD49f is similarly distributed between naïve and memory Tregs and impacts the expression of CD39, CTLA-4, FoxP3 and CCR6 specifically in the memory compartment. Accumulation of CD49f high memory Tregs in the blood of ulcerative colitis patients correlates with disease severity. Our results highlight important considerations for Treg immunotherapy design in patients with inflammatory bowel disease which could possibly extend to other autoimmune disorders.
2021-08-06 | PXD022095 | Pride
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:Naïve CD4, Th17 (TGFB+IL6), Th17 (TGFb+IL6) + PAM3CSK4, and Th17 (TGFB+IL6) + biglycan samples were sequenced after 3d differentiation
2021-05-15 | GSE174469 | GEO
Project description:Background: Regulatory T cells (Tregs) are protective in atherosclerosis but reduced during disease progression due to cell death and loss of stability. However, the mechanisms of Treg dysfunction remain unknown. Oxidized phospholipids (oxPLs) are abundant in atherosclerosis and can activate innate immune cells, but little is known regarding their impact on T cells. Given Treg loss during atherosclerosis progression and oxPL levels in the plaque microenvironment, we investigated whether oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), an oxPL associated with atherosclerotic plaques, alters Treg differentiation and function. Methods: CD4+ T cells were polarized to Treg, Th1, and Th17 cells with or without oxPAPC and assessed by flow cytometry. Gene expression in oxPAPC-treated Tregs was analyzed by bulk RNA sequencing. Functional studies of oxPAPC-induced Tregs were performed by co-culturing Tregs with CTV-labeled cells in vitro, and by adoptively transferring Tregs to hyperlipidemic Ldlr-/- mice to measure atherosclerosis progression. Results: Compared to controls, oxPAPC-treated Tregs were less viable, but surviving cells expressed higher levels of the Th1-associated markers T-bet, CXCR3, and IFN-. Th1 and Th17 skewing cultures were unaltered by oxPAPC. IFN- is linked to Treg instability, thus Treg polarization experiments were repeated using Ifngr1-/- CD4+ T cells. IFNR1 deficiency did not improve cell viability in oxPAPC-treated Tregs, however, T-bet and IFN- expression was not increased in surviving cells suggesting a role for IFN-signaling. OxPAPC-treated Tregs were less suppressive in vitro, and adoptive transfer studies in hyperlipidemic Ldlr-/- mice showed that oxPAPC-induced Tregs possessed altered tissue homing and were insufficient to inhibit atherosclerosis progression. Conclusions: OxPAPC elicits Treg-specific changes altering Treg differentiation and inducing a Th1-like phenotype in surviving cells partially through IFN- signaling. This is biologically relevant as oxPAPC-treated Tregs do not reduce atherosclerosis progression in Ldlr-/- mice. This study supports the role for oxPLs in negatively impacting Treg differentiation and atheroprotective function.
2023-07-04 | GSE236226 | 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.
2014-12-12 | GSE56299 | GEO
Project description:The colonic lamina propria contains a distinct population of Foxp3+ T regulatory cells (Tregs) that modulate responses to commensal microbes. Analysis of gene expression revealed that the transcriptome of colonic Tregs is distinct from splenic and other tissue Tregs. Rorγ and Helios in colonic Tregs mark distinct populations: Rorγ+Helios- or Rorγ-Helios+ Tregs. We uncovered an unanticipated role for Rorγ, a transcription factor generally considered to be antagonistic to Foxp3. Rorγ in colonic Tregs accounts for a small but specific part of the colon-specific Treg signature. Nrp1- Tregs were sorted from Foxp3-cre.Rorcfl/fl mice, which have a Treg-selective deletion of Rorc, or paired WT littermates. For low-input RNAseq, 1,000 TCRb+CD4+YFP(Foxp3)+Nrp1- cells were double-sorted into Trizol, RNA extracted and reverse-transcribed using ArrayScript (Ambion). To reduce variability at least three replicates were generated.
2015-07-25 | E-GEOD-71304 | biostudies-arrayexpress