HDAC10 deletion in Treg
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ABSTRACT:
PROVIDER: PRJNA544959 | ENA |
REPOSITORIES: ENA
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Project description:Treg cells and Treg-specific deletion of Blimp1
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Project description:Mef2d, Mef2c, HDAC1, HDAC2 and Dyrk1 are involved with Foxp3 Treg regulation. Conditional deletion of either gene in Foxp3 Treg (cre/loxP) was generated and RNA sequenced and analyzed via Novogene, Inc.
2019-10-29 | GSE139480 | GEO
Project description:The inflammasome initiates innate defense and inflammatory response by activating caspase-1 and pyroptotic cell death in myeloid cells1,2. It is comprised of an innate immune receptor/effector, pro-caspase-1 and a common adaptor molecule, ASC (apoptotic speck-containing protein with a CARD). Consistent with their pro-inflammatory function, inflammasome components including caspase-1, ASC and NLRP3, are known to exacerbate autoimmunity during experimental autoimmune encephalomyelitis (EAE) by enhancing IL-1 and IL-18 secretion in myeloid cells3-6. Here we show an unexpected function of a DNA-binding inflammasome effector, AIM2 (Absent in Melanoma 2)7-10, in restraining autoimmunity by performing EAE in both whole body and Treg-specific deletion of Aim2–/– mice. AIM2 is highly expressed by human and mouse Treg cells and it is essential to attenuate EAE. RNA-seq, biochemical and metabolic analyses revealed that AIM2 attenuates mTOR, Myc and immune-metabolic functions in both Treg cells isolated in vivo and Treg cells induced in vitro with TGF-. Importantly, we found AIM2 physically interacted with RACK1 in Treg cells to facility the PP2A/RACK1/Akt-mTOR signaling, which is identified as a central component downstream of AIM2 that controls Treg cell function and stability. While AIM2 is generally accepted as an inflammasome effector in myeloid cells, this report reveals a previously unappreciated T cell-intrinsic role of AIM2 in maintaining Treg cell function to restrain autoimmunity. This is achieved by diminishing Akt-mTOR signaling to regulate Treg stability under inflammation, and altering immune-metabolism in Treg cells.
2021-01-27 | PXD018638 | Pride
Project description:Foxp3+ T-regulatory (Treg) cells have well established roles in maintaining immune homeostasis and tolerance, but the contributions of several large multiprotein complexes that regulate gene expression remain unexplored in Tregs. We analyzed the role in Tregs of the evolutionarily conserved CoREST complex that consists of a scaffolding protein, Rcor1 or Rcor2, plus Hdac1, Hdac2 and Lsd1 enzymes. We found Rcor1, Rcor2 and Lsd1 were physically associated with Foxp3, and that mice with conditional deletion of Rcor1 in Foxp3+ Treg cells had decreased proportions of Tregs in their peripheral lymphoid tissues, and increased Treg expression of IL-2 and IFN-g compared to WT cells. In vivo, compared with WT mice, mice with conditional deletion of Rcor1 in their Tregs had reduced suppression of homeostatic proliferation, inability to maintain long-term allograft survival despite costimulation blockade, and enhanced antitumor immunity in syngeneic models. Comparable findings were seen in WT mice treated with a CoREST inhibitor. Our data point to the potential for therapeutic modulation of Treg functions by pharmacologic targeting of enzymatic components of the CoREST complex, and contribute to an understanding of the biochemical and molecular mechanisms by which Foxp3 represses large gene sets and maintains the unique properties of this key immune cell type.
2019-09-10 | GSE137137 | GEO
Project description:Whole transcriptome sequencing of Treg with and without Rcor1 deletion
| PRJNA564613 | ENA
Project description:Regulatory T (Treg) cells characterized by expression of the transcription factor forkhead box P3 (Foxp3) maintain immune homeostasis by suppressing self-destructive immune responses1-4. Foxp3 operates as a late acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg cell lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6-10. However, whether Foxo proteins act beyond the Treg cell commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1, and display reduced T-cell receptor-induced Akt activation, Foxo1 phosphorylation, and Foxo1 nuclear exclusion. Mice with Treg cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the proinflammatory cytokine Ifng, that do not appear to be directly regulated by Foxp3. These findings demonstrate that the evolutionarily ancient Akt-Foxo1 signaling module controls a novel genetic program indispensable for Treg cell function. Treg cells were isolated from wild-type B6 mice or Foxo1tagBirA mice in which foxo1 is endogenously biotinylated. Foxo1 binding targets in Treg cells were identified by using Foxo1 antibody- and Streptavidin- ChIP-Seq approaches.
2012-09-07 | E-GEOD-40656 | biostudies-arrayexpress
Project description:We observed that mice with the Treg-specific deletion of Blimp1 had delayed and smaller tumor growth associated with the activation of tumor-infiltrating immune effector cells. To determine what extent disruptions of Treg suppressive activity by a specific deletion of Blimp1 could impact on the tumor, we assessed the gene expression of sorted tumor cells by NanoString analysis.
2021-11-24 | GSE178134 | GEO
Project description:We observed that mice with the Treg-specific deletion of Blimp1 had delayed and smaller tumor growth associated with the activation of tumor-infiltrating immune effector cells. To determine what extent disruptions of Treg suppressive activity by a specific deletion of Blimp1 could impact on the tumor, we assessed the gene expression of sorted tumor cells by NanoString analysis.
2021-11-24 | GSE178133 | GEO
Project description:Changes in Treg gene expression upon deletion of Usp22 and Usp21
| PRJNA857304 | ENA
Project description:HDAC10–/– (B6N(Cg)-Hdac10tm1.1(KOMP)Mbp/J) and wild type (WT) CD4+CD25+ Treg were isolated and RNA procured. Single strand cDNA was generated, fragmented and labeled, and hybridized to Affymetrix GeneChip Mouse Gene 2.0 ST Arrays for microarray analysis.
2019-05-28 | GSE131794 | GEO