What question did this study set out to answer?

This research aims to understand the changes in beta cell senescence and inflammation during the progression of type 1 diabetes and the impact of anti-CD3 therapy.

June 7, 2026

2676-P: Temporal, Spatial, and Immune Modulation of β-Cell Senescence, Identity, and Inflammation during Type 1 Diabetes Progression

Key Points

This research aims to understand the changes in beta cell senescence and inflammation during the progression of type 1 diabetes and the impact of anti-CD3 therapy.
Analyzed scRNA-seq data from islets of 4-14-week-old female NOD mice to assess beta cell senescence and inflammation.
Conducted GeoMx Digital Spatial Profiling on islet regions categorized by insulitis severity in treated mice.
Performed differential gene expression and pathway enrichment analyses to explore transcriptional changes.
Beta cell senescence increased gradually as type 1 diabetes progressed, along with inflammatory signatures.
Severe-insulitis islets demonstrated higher senescence and inflammation with decreased beta cell identity genes.
aCD3 treatment led to reduced severe-insulitis regions, increased beta cell numbers, and shifted transcriptional profiles toward metabolic pathways.

Abstract

Introduction and Objective: Senescence of β cells occurs in type 1 diabetes (T1D); however, how senescence-associated β cell identity and inflammatory programs evolve across disease progression, inflammatory niches, and immunomodulatory treatments is unknown. In this study, we defined the temporal and spatial transcriptional dynamics of β cell senescence, identity, and inflammation during T1D progression and following anti-CD3 (aCD3) therapy. Methods: scRNA-seq data of islets from 4-14-week-old female NOD mice were analyzed to quantify β cell senescence, identity, and inflammatory transcriptional programs using curated gene modules. We performed GeoMx Digital Spatial Profiling of islet regions stratified by insulitis severity in aCD3- or IgG-treated NOD mice and differential gene expression and pathway enrichment analyses. Results: scRNA-seq revealed gradual increases in β cell senescence and inflammatory signature genes with disease progression. Despite rising senescence, β cell identity gene programs remained preserved at early stages. Senescence intensity stratification showed that senescence was associated with a decline in β cell identity at later stages. Spatial profiling showed that β cells within severe-insulitis islets exhibited elevated senescence and inflammatory signaling with reduced β cell identity genes, whereas non-insulitis islets maintained intact transcriptional profiles. aCD3 treatment reduced severe-insulitis regions, increased β cell numbers, decreased senescence and inflammatory gene programs in β cells, and shifted transcriptional profiles toward metabolic and homeostatic pathways. Conclusion: These studies indicate that β cell senescence is a dynamic process shaped by disease stage, inflammatory context, and immune pressure. aCD3 therapy reduces senescence-associated inflammatory and identity alterations, supporting coordinated temporal, spatial, and immune regulation of β cell states in T1D. Disclosure J. Lee: None. R.B. Kang: None. A. Garcia-Ocana: Advisory Panel; Current; Paulex Bio. G. Lu: None. Funding NIH-NIDDK (DK105015)

Mark Helpful

Bookmark

Relay