The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes

Thomas Hill; Olga Krougly; Enayat Nikoopour; Stacey Bellemore; Edwin Lee-Chan; Lynette A Fouser; David J Hill; Bhagirath Singh

doi:10.1186/2045-9769-2-2

The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes

Cell Regen. 2013 Apr 4;2(1):2. doi: 10.1186/2045-9769-2-2. eCollection 2013.

Authors

Thomas Hill¹, Olga Krougly¹, Enayat Nikoopour¹, Stacey Bellemore¹, Edwin Lee-Chan¹, Lynette A Fouser², David J Hill³, Bhagirath Singh⁴

Affiliations

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 ; Lawson Health Research Institute, London, ON Canada.
⁴ Department of Microbiology and Immunology, University of Western Ontario, London, ON Canada ; Centre for Human Immunology, University of Western Ontario, London, ON Canada ; Robarts Research Institute, University of Western Ontario, London, ON Canada.

Abstract

Background: 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.

Results: 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.

Conclusions: We conclude that IL-22 may contribute to the regeneration of β-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.

Keywords: Adjuvant immunotherapy; Beta-cell regeneration; Interleukin-22; Regenerating (Reg) genes; Type 1 diabetes.