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

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

机构地区：[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

出　　处：《Cell Regeneration》2013年第1期7-17,共11页细胞再生（英文）

基　　金：We thank Ms.Brenda Strutt and Jessica Hill for technical help and Dr.Margery Ma from Pfizer,Cambridge,MA for anti-IL-22 antibody.We also thank Dr.Kathleen Hill,Dr.Alexander Timoshenko and Morgan Kleiber for assistance in experimental design and interpretation of the data.This work was supported by grants from the Canadian Institutes of Health Research(CIHR).

摘　　要：Background:In Type 1 diabetes,the insulin-producingβ-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 pancreaticβ-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)-αmRNA 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-22Rαfollowing 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 isletβ-cell DNA synthesis in vitro in the presence of IL-22.Conclusions:We conclude that IL-22 may contribute to the regeneration ofβ-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.

关 键 词：Adjuvant immunotherapy INTERLEUKIN-22 Regenerating(Reg)genes Beta-cell regeneration Type 1 diabetes 

分 类 号：R73[医药卫生—肿瘤]