What question did this study set out to answer?

This study aims to understand how interferon signaling through STAT1 affects antiviral activities and gene expression in β-cells.

June 7, 2026

2691-P: Role of Stat1 in β-Cell Antipathogen Responses

Key Points

This study aims to understand how interferon signaling through STAT1 affects antiviral activities and gene expression in β-cells.
Mice with β-cell conditional deletion of STAT1 and wildtype mice received Poly(I:C) injections.
Islets were harvested 3-24 hours post-injection for gene expression evaluation via qRT-PCR and scRNAseq.
EMCV replication was measured in islets from wildtype and STAT1 KO mice 6 hours post administration.
Poly(I:C) administration transiently increases antibacterial, antiviral, and antioxidant gene expression in islets at 3 hours, returning to basal levels by 24 hours.
EMCV replication is inhibited in islets from wildtype mice but not in those from STAT1 KO mice 6 hours post Poly(I:C) administration.

Abstract

Introduction and Objective: While cytokines are believed to contribute to the destruction of β-cells and subsequent development of T1D, we have identified a physiological role of cytokine signaling that functions to protect the endocrine pancreas from pathogens. These pathways were elucidated using a novel in vivo model of cytokine signaling in the endocrine pancreas. In this study we aim to understand the role of interferon signaling through STAT1 in the control of antipathogen gene expression and antiviral activities in β-cells. Methods: Mice harboring a β-cell conditional deletion of STAT1 and wildtype mice received IP injections of 12mg/kg dose Poly(I:C). Islets were harvested 3-24 hours post injection, and the gene responses of these islets were evaluated via qRT-PCR and scRNAseq. The functional effects were evaluated by measuring EMCV replication in islets isolated from wildtype and STAT1 KO mice 6 h post Poly(I:C) administration. Results: In response to Poly(I:C) administration, a molecular PAMP that stimulates the production of multiple proinflammatory cytokines, there is a transient increase in the expression of antibacterial, antiviral, and antioxidant genes in islets that is first detected as early as 3 hours post administration and that returns to basal levels by 24 hours post injection. Functionally, EMCV replication is inhibited in islets isolated from wildtype control mice administered with Poly(I:C), while this inhibition of virus replication is lost in islets isolated from Stat1 KO mice 6 h post Poly(I:C) administration. Conclusion: These findings show that interferon signaling through STAT1 is necessary for stimulating protective and antipathogen gene expression that functions to limit viral replication in β-cells. These findings also begin to provide experimental data supporting the novel hypothesis that there are physiological roles for cytokine signaling in endocrine cells that function to protect β-cells from damage and destruction associated with the invading pathogen. Disclosure K. Harty: None. J. Bartosiak: None. P. Hansen: None. J. Corbett: None.

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