ArticleDiabetes2015
Inflammation and hyperglycemia mediate Deaf1 splicing in the pancreatic lymph nodes via distinct pathways during type 1 diabetes.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Expression-Based Genome-Wide Association Study Links Vitamin D-Binding Protein With Autoantigenicity in Type 1 Diabetes.Diabetes · 2016Pooled it
- The impact of donor diabetes on corneal transplant immunity.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes.Cell & bioscience · 2023Review
- Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis.Scientific reports · 2022Article
- SRSF10: an atypical splicing regulator with critical roles in stress response, organ development, and viral replication.RNA (New York, N.Y.) · 2021Review
- Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8Diabetes · 2021Article
- CCL21 Expression in β-Cells Induces Antigen-Expressing Stromal Cell Networks in the Pancreas and Prevents Autoimmune Diabetes in Mice.Diabetes · 2019Article
- GWAS for Meat and Carcass Traits Using Imputed Sequence Level Genotypes in Pooled F2-Designs in Pigs.G3 (Bethesda, Md.) · 2019Article
- Cell Based Therapy for Type 1 Diabetes: Should We Take Hyperglycemia Into Account?Frontiers in immunology · 2019Review
- Altered Function of Antigen-Presenting Cells in Type 1 Diabetes: A Challenge for Antigen-Specific Immunotherapy?Diabetes · 2018Review
- Genome-wide DNA methylome alterations in acute coronary syndrome.International journal of molecular medicine · 2018Article
- Impact of blood collection and processing on peripheral blood gene expression profiling in type 1 diabetes.BMC genomics · 2017Article
- MECHANISMS IN ENDOCRINOLOGY: Alternative splicing: the new frontier in diabetes research.European journal of endocrinology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Peripheral tolerance is partially controlled by the expression of peripheral tissue antigens (PTAs) in lymph node stromal cells (LNSCs). We previously identified a transcriptional regulator, deformed epidermal autoregulatory factor 1 (Deaf1), that can regulate PTA expression in LNSCs of the pancreatic lymph nodes (PLNs). During the pathogenesis of type 1 diabetes (T1D), Deaf1 is spliced to form the dominant-negative isoform Deaf1-Var1. Here we show that Deaf1-Var1 expression correlates with the severity of disease in NOD mice and is reduced in the PLNs of mice that do not develop hyperglycemia. Inflammation and hyperglycemia independently drive Deaf1 splicing through activation of the splicing factors Srsf10 and Ptbp2, respectively. Inflammation induced by injection of activated splenocytes increased Deaf1-Var1 and Srsf10, but not Ptbp2, in the PLNs of NOD.SCID mice. Hyperglycemia induced by treatment with the insulin receptor agonist S961 increased Deaf1-Var1 and Ptbp2, but not Srsf10, in the PLNs of NOD.B10 and NOD mice. Overexpression of PTBP2 and/or SRSF10 also increased human DEAF1-VAR1 and reduced PTA expression in HEK293T cells. These data suggest that during the progression of T1D, inflammation and hyperglycemia mediate the splicing of DEAF1 and loss of PTA expression in LNSCs by regulating the expression of SRSF10 and PTBP2.
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