ImmGen cytokines: Signatures of “common γ-chain” family cytokines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA746283 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Profiling of early in-vivo responses to the 6 common gamma-chain family cytokines, in 14 immunologic cell-types.
2022-01-01 | GSE180020 | GEO
Project description:"γc" cytokines are a family whose receptors share a “common gamma chain” signaling moiety, and play central roles in the differentiation, homeostasis and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines, across all immunocyte lineages. The results show a different response landscape than expected: broader, with a strong Myc-controlled resetting of biosynthetic and metabolic pathways, a major downregulation component, and extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere). Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises are uncovered: IL2 effects in mast cells, major shifts between follicular and marginal-zone B cells, paradoxical and cell-specific cross-talk between IFN and γc signaling, or an NK-T like program induced by IL21 in CD8+ T cells.
2022-07-22 | GSE208138 | GEO
Project description:Analysis of how different gamma chain family cytokines influence CD8 T cell differentiation.
2014-06-06 | GSE58262 | GEO
Project description:Analysis of how different gamma chain family cytokines influence CD8 T cell differentiation. Naïve CD8 T cells were isolated from the spleens OT-I Thy1.1 TCR Tg mice. Whole splenocytes from wild-type C57BL/6 mice were used as stimulator cells. Purified naïve wild-type OT-I (1×106/well) were stimulated with OVA peptide (SIINFEKL) pulsed (5 µg/ml) and irradiated (2,000 rads) syngeneic splenocytes (6×106/well) in 24-well plates. Forty-eight hours later, activated OT-I T cells were harvested and viable cells were enriched over a Ficoll-paque gradient and washed with cRPMI prior to being reseeded in cRPMI (5×105 cells/ml) and treated with the media supplemented with various γc cytokines (IL-2, IL-4, IL-7, IL-15 and IL-21). Experimental samples were treated with 100 ng/ml of their respective gamma chain cytokine and incubated at 37ºC for 24 hours. RNA was isolated using either the RNeasy Mini kit, or a combination of TRIzol reagent and the Direct-zol RNA miniprep kit, all following manufacturer protocols. Two biological replicates for mRNA analysis were prepped using the RNeasy kit. The third replicate was prepped using the Trizol/Direct-zol approach. The quality and quantity of RNA samples was further analyzed on the Bioanalyzer. Labeled target cDNA was prepared from total RNA samples using the Ambion MessageAmp Premier protocol (3’IVT assay). Each sample target was hybridized to a Mouse 430 2.0 GeneChip array. Image processing and expression analysis were performed using Affymetrix GeneChip Command Console (AGCC) v. 3.1.1 and Affymetrix Expression Console v.1.1 software, respectively. Data from all biological replicates and conditions was imported into the Affymetrix Expression Console and normalized (RMA). RNA processing and microarray hybridization were performed by the Oregon Health & Science University Gene Microarray Shared Resource core facility in Portland, Oregon.
2014-06-06 | E-GEOD-58262 | biostudies-arrayexpress
Project description:The common γ chain (γc; IL2RG) is a subunit of the interleukin (IL) receptors for the γc cytokines IL2, IL4, IL7, IL9, IL15, and IL21. Because of the lack of appropriate neutralizing antibodies recognizing IL2RG, it has been difficult to thoroughly interrogate the role of γc cytokines in inflammatory and autoimmune disease settings. To determine whether γc cytokines might be targeted for T-cell-mediated disease prevention and treatment, we generated a new γc cytokine receptor antibody, REGN7257. Biochemical, structural and in vitro analysis showed that REGN7257 binds with high affinity to IL2RG and potently blocks signaling of all γc cytokines. In nonhuman primates, REGN7257 efficiently suppressed T-cells without impacting granulocytes, platelets or red blood cells. Using REGN7257, we showed that γc cytokines drive T-cell-mediated disease in mouse models of graft-versus-host disease (GVHD) and multiple sclerosis, by impacting multiple aspects of the pathogenic response. Importantly, we discovered that our xenogeneic GVHD mouse model recapitulates hallmarks of both acute and chronic GVHD, with T-cell expansion/infiltration into tissues and liver fibrosis, as well as hallmarks of immune aplastic anemia, with bone marrow aplasia and peripheral cytopenia. And we showed that γc cytokines contribute to disease pathology by driving all of these features. Overall, by demonstrating that broad inhibition of γc cytokine signaling with REGN7257 protects from immune-mediated disorders, our data provide evidence of γc cytokines as key drivers of pathogenic T-cell responses, offering a potentially novel strategy for the management of T-cell-mediated diseases.
2022-10-04 | GSE214625 | GEO
Project description:In the context of T1 Diabetes, pro-inflammatory cytokines IL-1β and IFN-γ are known to contribute to β-cell apoptosis; The measurement of mRNA expression following β-cell exposure to these cytokines gives a picture of the changes in gene expression characterizing the path to β-cell dysfunction and death. Human islets were isolated and exposed (or not) to IL-1β and IFN-γ. The samples were collected at various time points for profiling with Affymetrix arrays. These measurements were performed three times.
2013-12-19 | E-GEOD-53454 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4710466 | biostudies-literature
Project description: Not available
| S-EPMC3471675 | biostudies-literature