Project description:Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis – for example, metabolism and repair. Dedicated Treg compartments – with distinct transcriptomes, T-cell-receptor repertoires, and growth/survival factor dependencies – have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue – when, where and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor, PPARg, contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARg, the “master-regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARglo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, e.g. skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens new possibilities for regulating their emergence experimentally or therapeutically.
2021-03-11 | GSE168607 | GEO
Project description:Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis – for example, metabolism and repair. Dedicated Treg compartments – with distinct transcriptomes, T-cell-receptor repertoires, and growth/survival factor dependencies – have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue – when, where and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor, PPARg, contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARg, the “master-regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARglo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, e.g. skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens new possibilities for regulating their emergence experimentally or therapeutically.
2021-03-11 | GSE168606 | GEO
Project description:Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis – for example, metabolism and repair. Dedicated Treg compartments – with distinct transcriptomes, T-cell-receptor repertoires, and growth/survival factor dependencies – have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue – when, where and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor, PPARg, contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARg, the “master-regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARglo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, e.g. skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens new possibilities for regulating their emergence experimentally or therapeutically.
2021-03-11 | GSE168605 | GEO
Project description:Gene expression profiling of Bone Marrow FoxP3+ Treg cells. Glatman Zaretsky et al. revealed an unexpected role for Tregs in plasma cell biology. Here we determined the gene-expression profile of this new subset of FoxP3+ Treg cell, which express high levels of Treg effector molecules, similar to other non-lymphoid tissue Tregs. Gene-profiling of BM Tregs. Bone marrow Treg cells (30k) (gfp+CD25hiCD4+TCRβ+) (dump negative: CD19-CD8α-TCRγδ-CD11b-CD11c-NK1.1-Gr-1-Ter-119-) were triple-sorted from pools of two to three reporter mice (C57BL/6 Foxp3-IRES-gfp, 9 week-old males) into trizol per ImmGen SOP. RNA was amplified, labeled and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays (Expression Analysis)
2015-12-23 | E-GEOD-76264 | biostudies-arrayexpress
Project description:Gene expression profiling of Bone Marrow FoxP3+ Treg cells. Glatman Zaretsky et al. revealed an unexpected role for Tregs in plasma cell biology. Here we determined the gene-expression profile of this new subset of FoxP3+ Treg cell, which express high levels of Treg effector molecules, similar to other non-lymphoid tissue Tregs.
2015-12-23 | GSE76264 | GEO
Project description:Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Only 12% of 422 differentially expressed proteins was identified as such at the mRNA level, demonstrating the importance of direct proteome measurement. Fifty-one proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFB-, PI3 kinase/mTOR-, NFAT- and STAT pathways, and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, whereas transitional FOXP3+ cells can. Collectively, our data reveal that Treg identity is defined and protected by uniquely “wired” signaling pathways. Associated GEO dataset is available at GSE90600.
2018-05-18 | PXD007744 | Pride
Project description:Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Only 12% of 422 differentially expressed proteins was identified as such at the mRNA level, demonstrating the importance of direct proteome measurement. Fifty-one proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFB-, PI3 kinase/mTOR-, NFAT- and STAT pathways, and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, whereas transitional FOXP3+ cells can. Collectively, our data reveal that Treg identity is defined and protected by uniquely “wired” signaling pathways.
2018-05-18 | PXD005477 | Pride
Project description:Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Only 12% of 422 differentially expressed proteins was identified as such at the mRNA level, demonstrating the importance of direct proteome measurement. Fifty-one proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFB-, PI3 kinase/mTOR-, NFAT- and STAT pathways, and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, whereas transitional FOXP3+ cells can. Collectively, our data reveal that Treg identity is defined and protected by uniquely “wired” signaling pathways.
2018-05-18 | PXD007745 | Pride
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:The proposed use of Foxp3+ T-regulatory (Treg) cells as potential cellular therapy in patients with autoimmune diseases, or post-hemopoietic stem cell or organ transplantation, requires a sound understanding of the transcriptional regulation of Foxp3 expression. Conserved CpG dinucleotides in the Treg-specific demethylated region (TSDR) upstream of Foxp3 are demethylated only in stable, thymic-derived Foxp3+ Tregs. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling complexes to methylated sites, we tested whether targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg numbers or function. Surprisingly, while ChIP analysis showed Mbd2 binding to the Foxp3-associated TSDR site in Tregs, Mbd2 targeting by homologous recombination or siRNA decreased Treg numbers and impaired Treg suppressive function in vitro and in vivo. Moreover, we found complete TSDR demethylation in WT Tregs but >75% methylation in Mbd2-/- Tregs, whereas re-introduction of Mbd2 into Mbd2-null Tregs restored TSDR demethylation, Foxp3 gene expression and Treg suppressive function. Lastly, Mbd2-/- Tregs had markedly binding of the DNA demethylase enzyme, Tet2, in the TSDR region. These data show that Mbd2 has a key role in promoting TSDR demethylation, Foxp3 expression and Treg suppressive function. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of MBD2–/– mice, compared to wild type control (all Balb/c background).
2013-09-01 | E-GEOD-48653 | biostudies-arrayexpress
