Shifts in Isoform Usage Underlie Transcriptional Differences in Regulatory T Cells in Type 1 Diabetes

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Sep 27

PMID 37758901

Authors

Jeremy R B Newman

S Alice Long

Cate Speake

Carla J Greenbaum

Karen Cerosaletti

Stephen S Rich

Suna Onengut-Gumuscu

Lauren M McIntyre

Jane H Buckner

Patrick Concannon

Affiliations

Soon will be listed here.

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. Here we assay gene expression between T1D cases and healthy controls in two autoimmunity-relevant lymphocyte cell types, memory CD4/CD25 regulatory T 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 are observed in memory CD4/CD25 T-cells. In Tregs, 402 genes demonstrate 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 pathophysiology.

Citing Articles

Shifts in isoform usage underlie transcriptional differences in regulatory T cells in type 1 diabetes.

Newman J, Long S, Speake C, Greenbaum C, Cerosaletti K, Rich S Commun Biol. 2023; 6(1):988.

PMID: 37758901 PMC: 10533491. DOI: 10.1038/s42003-023-05327-7.

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