Abstract

The IL-22RA1 receptor is highly expressed in the pancreas, and exogenous IL-22 has been shown to reduce endoplasmic reticulum and oxidative stress in human pancreatic islets and promote secretion of high-quality insulin from beta-cells. However, the endogenous role of IL-22RA1 signaling on these cells remains unclear. Here, we show that antibody neutralisation of IL-22RA1 in cultured human islets leads to impaired insulin quality and increased cellular stress. Through the generation of mice lacking IL-22ra1 specifically on pancreatic alpha- or beta-cells, we demonstrate that ablation of murine beta-cell IL-22ra1 leads to similar decreases in insulin secretion, quality and islet regeneration, whilst increasing islet cellular stress, inflammation and MHC II expression. These changes in insulin secretion led to impaired glucose tolerance, a finding more pronounced in female animals compared to males. Our findings attribute a regulatory role for endogenous pancreatic beta-cell IL-22ra1 in ...

Authors	Sajiir, H; Wong, KY; Müller, A; Keshvari, S; Burr, L; Aiello, E; Mezza, T; Giaccari, A; Sebastiani, G; Dotta, F; Ramm, GA; Macdonald, GA; McGuckin, MA; Prins, JB; Hasnain, SZ
Journal	Nature Communications
Pages	4527
Volume	15
Date	29/06/2024
Grant ID	Ideas Grant | Department of Health | National Health and Medical Research Council (NHMRC); Developmental Grant | Department of Health | National Health and Medical Research Council (NHMRC); Clinical Collaborative Grant | Gastroenterological Society of Australia (GESA)
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41467-024-48320-2