Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA112333 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Deletional Tolerance Mediated by Extrathymic Aire-Expressing Cells
| PRJNA113139 | ENA
Project description:Peripheral tolerance induction is critical for the maintenance of self-tolerance and can be mediated by immunoregulatory T cells or by direct induction of T cell anergy or deletion. While the molecular processes underlying anergy have been extensively studied, little is known about the molecular basis for peripheral T cell deletion. Here, we determined the gene expression signature of peripheral CD8+ T cells undergoing deletional tolerance, relative to those undergoing immunogenic priming or lymphopenia-induced proliferation. From these data, we report the first detailed molecular signature of cells undergoing deletion. Consistent with defective cytolysis, these cells exhibited deficiencies in granzyme up-regulation. Furthermore, they showed antigen-driven Bcl-2 down-regulation and early up-regulation of the pro-apoptotic protein Bim, consistent with the requirement of this BH3-only protein for peripheral T cell deletion. Bim up-regulation was paralleled by defective IL-7Ra chain re-expression, suggesting that Bim-dependent death may be triggered by loss of IL-7/IL-7R signaling. Finally, we observed parallels in molecular signatures between deletion and anergy suggesting that these tolerance pathways may not be as molecularly distinct as previously surmised. Naïve (CD44lo) OT-I T cells were CFSE labelled and transferred in a model of deletional tolerance (RIP-OVAhi mice), a model of immunity (mice primed with OVA coated splenocytes and LPS) or a model of lymphopenia induced proliferation (Rag-/- mice). 60 hrs (RIP-OVAhi and OVA coated splenocytes) or 5 days (Rag-/-) after transfer, OT-I cells that had undergone two or more divisions as determined by CFSE dilution were sorted, RNA extracted and samples were prepared for hybridisation to Affymetrix microarrays. As a control for naive cells, CFSE labelled OT-I cells were injected into antigen-free B6 mice and the undivided naive cells were sorted after 60 hrs and also used for microarray analysis. Two replicates were prepared for the naive cells, cells from RIP-OVAhi mice and cells from OVA coated splenocyte primed mice, while one replicate was prepared for the cells from Rag-/- mice.
2009-02-10 | E-GEOD-14699 | biostudies-arrayexpress
Project description:Peripheral tolerance induction is critical for the maintenance of self-tolerance and can be mediated by immunoregulatory T cells or by direct induction of T cell anergy or deletion. While the molecular processes underlying anergy have been extensively studied, little is known about the molecular basis for peripheral T cell deletion. Here, we determined the gene expression signature of peripheral CD8+ T cells undergoing deletional tolerance, relative to those undergoing immunogenic priming or lymphopenia-induced proliferation. From these data, we report the first detailed molecular signature of cells undergoing deletion. Consistent with defective cytolysis, these cells exhibited deficiencies in granzyme up-regulation. Furthermore, they showed antigen-driven Bcl-2 down-regulation and early up-regulation of the pro-apoptotic protein Bim, consistent with the requirement of this BH3-only protein for peripheral T cell deletion. Bim up-regulation was paralleled by defective IL-7Ra chain re-expression, suggesting that Bim-dependent death may be triggered by loss of IL-7/IL-7R signaling. Finally, we observed parallels in molecular signatures between deletion and anergy suggesting that these tolerance pathways may not be as molecularly distinct as previously surmised.
2009-02-10 | GSE14699 | GEO
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
2014-12-04 | GSE61417 | GEO
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