The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes
1 Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
2 Inflammation and Immunology, Biotherapeutics Research and Development, Pfizer, Cambridge, MA, 02140, USA
3 Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
4 Lawson Health Research Institute, London, ON, Canada
5 Centre for Human Immunology, University of Western Ontario, London, ON, Canada
6 Robarts Research Institute, University of Western Ontario, London, ON, Canada
Cell Regeneration 2013, 2:2 doi:10.1186/2045-9769-2-2Published: 4 April 2013
In Type 1 diabetes, the insulin-producing β-cells within the pancreatic islets of Langerhans are destroyed. We showed previously that immunotherapy with Bacillus Calmette-Guerin (BCG) or complete Freund’s adjuvant (CFA) of non-obese diabetic (NOD) mice can prevent disease process and pancreatic β-cell loss. This was associated with increased islet Regenerating (Reg) genes expression, and elevated IL-22-producing Th17 T-cells in the pancreas.
We hypothesized that IL-22 was responsible for the increased Reg gene expression in the pancreas. We therefore quantified the Reg1, Reg2, and Reg3δ (INGAP) mRNA expression in isolated pre-diabetic NOD islets treated with IL-22. We measured IL-22, and IL-22 receptor(R)-α mRNA expression in the pancreas and spleen of pre-diabetic and diabetic NOD mice. Our results showed: 1) Reg1 and Reg2 mRNA abundance to be significantly increased in IL-22-treated islets in vitro; 2) IL-22 mRNA expression in the pre-diabetic mouse pancreas increased with time following CFA treatment; 3) a reduced expression of IL-22Rα following CFA treatment; 4) a down-regulation in Reg1 and Reg2 mRNA expression in the pancreas of pre-diabetic mice injected with an IL-22 neutralizing antibody; and 5) an increased islet β-cell DNA synthesis in vitro in the presence of IL-22.
We conclude that IL-22 may contribute to the regeneration of β-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.