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Open Access Research

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

Thomas Hill1, Olga Krougly1, Enayat Nikoopour1, Stacey Bellemore1, Edwin Lee-Chan1, Lynette A Fouser2, David J Hill34 and Bhagirath Singh156*

Author 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

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

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Cell Regeneration 2013, 2:2  doi:10.1186/2045-9769-2-2

Published: 4 April 2013

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; Interleukin-22; Regenerating (Reg) genes; Beta-cell regeneration; Type 1 diabetes