Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1223967 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Anti-CD3 mAb treatment reshapes infiltrating T and beta cells in the islets in autoimmune diabetes
| PRJNA1237897 | ENA
Project description:Anti-CD3 mAb delays or prevents type 1 diabetes (T1D) by modulating the immune mediated destruction of beta cells. Our findings described the reshaping of islet-infiltrating T cells and beta cells that lead to operational, but tenuous tolerance to autoimmune diabetes following anti-CD3 mAb treatment.
2025-03-24 | GSE292313 | GEO
Project description:Type 1 diabetes (T1D) results from autoimmune destruction of β cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas of diabetic NOD mice treated with anti-CD3 mAb and IL-1RA combination therapy. The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in the islets from cured mice.
2022-11-10 | PXD025394 | Pride
Project description:Type 1 Diabetes (T1D) is a chronic autoimmune disease resulting from T cell-mediated destruction of pancreatic beta cells. Although T cells are known to destroy beta cells, how they may impact non-lethal forms of beta cell stress that also contribute to T1D development is not known. Here, we established an intermittent treatment regimen using a validated monoclonal anti-CD3 antibody on the female nonobese diabetic (NOD) mouse model for T1D at late prediabetic stages that leads to depletion of antigen-specific T cells and improvement of glucose tolerance. We used mRNA-seq to explore transcriptomic changes in isolated pancreatic islets from mice treated with anti-CD3 antibody or IgG as a control.
2025-06-13 | GSE275350 | GEO
Project description:Type 1 diabetes (T1D) results from autoimmune destruction of β-cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas from diabetic NOD mice treated with anti-CD3 monoclonal antibody and IL-1 receptor antagonist (IL-1RA). The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in islets from mice with reversed diabetes. To address the functional role of PTPN2 in β-cells, we generated PTPN2 deficient stem cell-derived β-like and human EndoC-βH1 cells. Mechanistically, we demonstrated that PTPN2 inactivation in β-cells exacerbates the type I and type II IFN signalling networks, and the potential progression towards autoimmunity. Moreover, we established the capacity of PTPN2 to modulate the Ca2+-dependent unfolded protein response in β-cells. Adenovirus-induced overexpression of PTPN2 decreased BiP expression and partially protected from ER-stress induced β-cell death. Our results postulate PTPN2 as a key protective factor in β-cells during inflammation and ER stress in autoimmune diabetes.
2022-01-21 | GSE172148 | GEO
Project description:Several clinical trials have shown anti-CD3 treatment to be a promising therapy for autoimmune diabetes, but its mechanism of action remains unclear. Foxp3+ regulatory T (Treg) cells are likely to be involved, and we have shown a strong effect of anti-CD3 on homeostatic control of CD4+ FoxP3+ regulatory T (Treg) cells. To analyze the early consequences of anti-CD3 treatment, we sorted and profiled Treg and conventional CD4+ T (Tconv) cells in the first hours and days after anti-CD3 treatment of NOD mice. In practice, NOD mice carrying the Foxp3-GFP reporter were treated with anti-CD3 mAb KT3 (50 ug iv) and CD4+ T cells were sorted from pooled spleen and lymph nodes after 2, 8, 24 and 72 hrs, separating Treg and Tconv cells on the basis of GFP expression. Anti-CD3 treatment led to a transient transcriptional response, terminating faster than most antigen-induced responses. Most transcripts were similarly induced in Treg and Tconv cells, but several were differential, in particular those encoding the IL7 receptor (IL7R) and transcription factors Id2/3 and Gfi1, upregulated in Treg but repressed in Tconv cells. In parallel experiments, we tested the effect of soluble anti-CD3 added to cultures of fresh splenocytes, sorting Treg and Tconv cells at the same time points. Many of the anti-CD3 elicited changes, and of the differential response observed in vivo, were also observed in vitro. Two independent replicate series; Treg and Tconv samples abbreviated TR and TC, respectively. Keywords: Transcriptional activation, TCR All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. RNA from 5 x 104 cells was amplified, labeled, and hybridized to Affymetrix ST1.0 Gene arrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.
2013-07-01 | E-GEOD-48210 | biostudies-arrayexpress
Project description:Several clinical trials have shown anti-CD3 treatment to be a promising therapy for autoimmune diabetes, but its mechanism of action remains unclear. Foxp3+ regulatory T (Treg) cells are likely to be involved, and we have shown a strong effect of anti-CD3 on homeostatic control of CD4+ FoxP3+ regulatory T (Treg) cells. To analyze the early consequences of anti-CD3 treatment, we sorted and profiled Treg and conventional CD4+ T (Tconv) cells in the first hours and days after anti-CD3 treatment of NOD mice. In practice, NOD mice carrying the Foxp3-GFP reporter were treated with anti-CD3 mAb KT3 (50 ug iv) and CD4+ T cells were sorted from pooled spleen and lymph nodes after 2, 8, 24 and 72 hrs, separating Treg and Tconv cells on the basis of GFP expression. Anti-CD3 treatment led to a transient transcriptional response, terminating faster than most antigen-induced responses. Most transcripts were similarly induced in Treg and Tconv cells, but several were differential, in particular those encoding the IL7 receptor (IL7R) and transcription factors Id2/3 and Gfi1, upregulated in Treg but repressed in Tconv cells. In parallel experiments, we tested the effect of soluble anti-CD3 added to cultures of fresh splenocytes, sorting Treg and Tconv cells at the same time points. Many of the anti-CD3 elicited changes, and of the differential response observed in vivo, were also observed in vitro. Two independent replicate series; Treg and Tconv samples abbreviated TR and TC, respectively. Keywords: Transcriptional activation, TCR
2013-07-01 | GSE48210 | GEO
Project description:In previous studies, we showed that Tet2 controls the responses of beta cells to inflammation in a model of autoimmune Type 1 diabetes, but the specific cell types affected by Tet2 loss in islets was not clear and the molecular mechanisms responsible for the autoimmune responses and beta cell death were unknown. We found that Tet2-deficient islets have fewer islet infiltrating lymphocytes beginning 8-10 weeks after bone marrow transplant, reduced activation of CD8+ T cells, and greater CD8+ T cell repertoire diversity. Transcription factor finding motifs for interferon responses factors and inflammatory signaling molecules were enriched in Tet2-responsive cis-regulatory elements across all KO islet endocrine cells, but we observed beta cell-specific enrichment of TFs modulating homeostatic or ER stress response pathways. To confirm the effects of TET2 in human islets, we induced ER stress with brefeldin A or thapsigargin and inhibited TET2 with Bobcat 339. Pharmacologic TET inhibition reduced expression of ER stress response genes, inflammatory responses, and stress-induced beta cell death. We conclude that Tet2(TET2) can regulate ER stress responses involved in beta cell killing in autoimmune/inflammatory settings.
2026-01-05 | GSE305093 | GEO
Project description:In previous studies, we showed that Tet2 controls the responses of beta cells to inflammation in a model of autoimmune Type 1 diabetes, but the specific cell types affected by Tet2 loss in islets was not clear and the molecular mechanisms responsible for the autoimmune responses and beta cell death were unknown. We found that Tet2-deficient islets have fewer islet infiltrating lymphocytes beginning 8-10 weeks after bone marrow transplant, reduced activation of CD8+ T cells, and greater CD8+ T cell repertoire diversity. Transcription factor finding motifs for interferon responses factors and inflammatory signaling molecules were enriched in Tet2-responsive cis-regulatory elements across all KO islet endocrine cells, but we observed beta cell-specific enrichment of TFs modulating homeostatic or ER stress response pathways. To confirm the effects of TET2 in human islets, we induced ER stress with brefeldin A or thapsigargin and inhibited TET2 with Bobcat 339. Pharmacologic TET inhibition reduced expression of ER stress response genes, inflammatory responses, and stress-induced beta cell death. We conclude that Tet2(TET2) can regulate ER stress responses involved in beta cell killing in autoimmune/inflammatory settings.
2026-01-05 | GSE305092 | GEO
Project description:In previous studies, we showed that Tet2 controls the responses of beta cells to inflammation in a model of autoimmune Type 1 diabetes, but the specific cell types affected by Tet2 loss in islets was not clear and the molecular mechanisms responsible for the autoimmune responses and beta cell death were unknown. We found that Tet2-deficient islets have fewer islet infiltrating lymphocytes beginning 8-10 weeks after bone marrow transplant, reduced activation of CD8+ T cells, and greater CD8+ T cell repertoire diversity. Transcription factor finding motifs for interferon responses factors and inflammatory signaling molecules were enriched in Tet2-responsive cis-regulatory elements across all KO islet endocrine cells, but we observed beta cell-specific enrichment of TFs modulating homeostatic or ER stress response pathways. To confirm the effects of TET2 in human islets, we induced ER stress with brefeldin A or thapsigargin and inhibited TET2 with Bobcat 339. Pharmacologic TET inhibition reduced expression of ER stress response genes, inflammatory responses, and stress-induced beta cell death. We conclude that Tet2(TET2) can regulate ER stress responses involved in beta cell killing in autoimmune/inflammatory settings.
2026-01-05 | GSE305091 | GEO