Shifts in isoform usage underlie transcriptional differences in regulatory T cells in type 1 diabetes
Year: 2023
Type: article
Study design: Observational Study
Abstract: Genome-wide association studies have identified numerous loci with allelic associations to Type 1 Diabetes (T1D) risk. Most disease-associated variants are enriched in regulatory sequences active in lymphoid cell types, suggesting that lymphocyte gene expression is altered in T1D. We assayed gene expression between T1D cases and healthy controls in two autoimmunity-relevant lymphocyte cell types, memory CD4+/CD25+ T-regulatory cells (Treg) and memory CD4+/CD25- T-cells, using a splicing event-based approach to characterize tissue-specific transcriptomes. Limited differences in isoform usage between T1D cases and controls were observed in memory CD4+/CD25- T-cells. In Tregs, 553 genes demonstrated differences in isoform usage between cases and controls, particularly RNA recognition and splicing factor genes. Many of these genes are regulated by the variable inclusion of exons that can trigger nonsense mediated decay. Our results suggest that dysregulation of gene expression, through shifts in alternative splicing in Tregs, contributes to T1D etiology.
Source: Communications Biology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,690
Awards: G1569359803, G1574792121, G1654614051, G3945798686, Novel T1D risk variants from genomic analyses in high risk families, G5582543259, Expression and proteomic characterization of risk loci in type 1 diabetes, Critical role for alternative splicing in conferring risk for type 1 diabetes, G8655437103, Immune Function and the Progression to Type 1 Diabetes
OpenAlex ID: W4387099283