Abstract
Exposure to proinflammatory cytokines is believed to contribute to pancreatic β-cell damage during diabetes development. Although some cytokine-mediated changes in islet gene expression are known, the heterogeneity of the response is not well-understood. After 6-h treatment with IL-1β and IFN-γ alone or together, mouse islets were subjected to single-cell RNA sequencing. Treatment with both cytokines together led to expression of inducible nitric oxide synthase mRNA (Nos2) and antiviral and immune-associated genes in a subset of β-cells. Interestingly, IL-1β alone activated antiviral genes. Subsets of δ- and α-cells expressed Nos2 and exhibited similar gene expression changes as β-cells, including increased expression of antiviral genes and repression of identity genes. Finally, cytokine responsiveness was inversely correlated with expression of genes encoding heat shock proteins. Our findings show that all islet endocrine cell types respond to cytokines, IL-1β induces the expression of protective genes, and cellular stress gene expression is associated with inhibition of cytokine signaling.
| Original language | English (US) |
|---|---|
| Article number | e202000949 |
| Journal | Life science alliance |
| Volume | 4 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2021 |
Funding
The authors thank Dr. Polly Hansen and Joshua Stafford (Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI) for technical assistance and Dr. Polly Hansen, Aaron Naatz, Joshua Stafford, and Chay Teng Yeo (Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI) for helpful discussions related to this project and for proofreading the manuscript. This research was completed in part with computational resources and technical support provided by the Research Computing Center at MCW. Funding: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant DK-052194 (to JA Corbett), the National Institute of Allergy and Infectious Diseases grant AI-044458 (to JA Corbett) and AI-125741 and AI-148403 (to W Cui), the Juvenile Diabetes Research Foundation grant SRA-2019-829-S-B (to JA Corbett), and a grant from the Medical College of Wisconsin Cancer Center (to JA Corbett). JS Stancill was supported by the National Heart, Lung, and Blood grant T32-HL134643. MY Kasmani was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant DK-127526 and is a member of the Medical Scientist Training Program at the Medical College of Wisconsin, which is partially supported by a training grant from the National Institute of General Medical Sciences (T32-GM080202). This work was also supported by gifts from the Scott Tilton Foundation and from the Forest County Potawatomi Foundation.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Health, Toxicology and Mutagenesis
- Plant Science
- Ecology
