CTLA4-Ig changed the gene expression associated with cellular movement in osteoclast precursors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE112896 | GEO | 2018/05/06
REPOSITORIES: GEO
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Project description:CTLA4-Ig changed the gene expression associated with cellular movement in osteoclast precursors
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Project description:During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naM-CM-/ve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. Time series. Human resting and activated T cell dUTP mRNA-Seq profiles were generated on Illumina HiSeq2500
2015-02-17 | E-GEOD-64712 | biostudies-arrayexpress
Project description:During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor.
2015-02-17 | GSE64712 | GEO
Project description:New measures are needed to predict type 1 diabetes disease trajectory. We have developed a sensitive array-based bioassay whereby patient plasma is used to induce transcription in healthy “reporter” leukocytes. Here we report a refined gene ontology-based inflammatory index (I.I.359) that is based upon expression levels of 359 transcripts identified in cross-sectional studies of new onset Type 1 diabetes patients and controls, where higher scores reflect greater inflammatory bias. We examined the relationship between I.I.359 measured at onset and the post-onset disease course in local patients as well as participants of the TrialNet CTLA4-Ig trial. In untreated patients, I.I.359 at baseline was highly variable and exhibited a significant inverse relationship with stimulated C-peptide AUC at 3, 6, 12, 18 and 24 months post-onset. Further, duration of the post-onset partial remission was negatively related to baseline I.I.359 and positively associated with the peripheral abundance of activated regulatory T cells (CD4+/CD45RA-/FoxP3high).
2018-07-19 | GSE102234 | GEO
Project description:Ctla4-/- mice suffer from a severe autoimmunity characterized by indiscriminate self-reactive T cell activation. Itk-/-Ctla4-/- (DKO) mice are protected from lethal autoimmunity despite a fulminant autoimmune process in the LNs as self-reative T cells fail to migrate to destroy tissues. We used microarray to identify underlying differences in gene expression that could account for lack of migration of DKO T cells into tissues. CD4+CD25neg T cells from 3 weeks old male Ctla4-/- or DKO mice were sorted in duplicates, RNA was extracted using TRIzol reagent and microarray analysis performed with the Affymetrix MoGene 1.0 ST array
2013-09-25 | E-GEOD-51099 | biostudies-arrayexpress
Project description:Ctla4-/- mice suffer from a severe autoimmunity characterized by indiscriminate self-reactive T cell activation. Itk-/-Ctla4-/- (DKO) mice are protected from lethal autoimmunity despite a fulminant autoimmune process in the LNs as self-reative T cells fail to migrate to destroy tissues. We used microarray to identify underlying differences in gene expression that could account for lack of migration of DKO T cells into tissues.
2013-09-25 | GSE51099 | GEO
Project description:Rattus norvegicus Ctla4, cytotoxic T-lymphocyte-associated protein 4 [Source:RGD Symbol;Acc:61975], is expressed in 3 baseline experiment(s);
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