Lipopolysaccharide-induced cytokine signaling activates a temporal innate defense program and represses pancreatic β-cell identity. J Biol Chem 2025 Dec;301(12):110811
Date
10/16/2025Pubmed ID
41093076Pubmed Central ID
PMC12663513DOI
10.1016/j.jbc.2025.110811Scopus ID
2-s2.0-105021476490 (requires institutional sign-in at Scopus site)Abstract
Cytokine exposure has been promoted as one cause for the loss of β-cell mass during the development of type 1 diabetes. While in vitro studies have shown that cytokines inhibit insulin secretion and induce islet degeneration, interventions targeting these soluble mediators have had limited success in preventing disease development in rodents and humans. To understand the in vivo actions of cytokines in the endocrine pancreas, we explored the transcriptional responses of islets to endogenously produced cytokines following immune stimulation with the bacterial pathogen-associated molecular pattern lipopolysaccharide. We found that endogenous cytokine production in response to lipopolysaccharide administration stimulates the rapid, time-dependent expression of antiviral, antibacterial, and antioxidant genes and represses the expression of β-cell identity factors in islets. Changes in gene expression are associated with similar changes in protein expression and the actions are transient, with a return to control levels of gene expression 24 h post lipopolysaccharide administration. In contrast to a role in diabetes development, our findings support a physiologically relevant and dynamic immune-endocrine communication axis that is characterized by a cytokine-initiated cell-intrinsic defense response in the endocrine pancreas that has evolved to enhance the fitness of these essential cells during host infection.
Author List
Bartosiak JT, Hansen PA, Schumacher EA, Harty KR, Stancill JS, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytokines
Gene Expression Regulation
Humans
Immunity, Innate
Insulin-Secreting Cells
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
Signal Transduction
