Liver NK1.1 cells and IL-22 promote pancreatic islets allograft survival in type 1 diabetic mice (TRAN2P.969)

Abstract We determined the role of liver NK1.1 cells in allograft survival. Pancreatic islets from BALB/c mice survived in a type 1 diabetic C57BL/6 mice liver up to 15-21 days (n=5, p=0.001). Anti NK1.1 but not isotype control antibody treatment of type 1 diabetic C57BL/6 mice before and after pancreatic islet transfer rejected graft within 3 days (n=5, p=0.001). Anti-NK1.1 antibody treatment enhanced IL-1β (45.13 ± 5.9 vs 94.25 ± 5.5; p = 0.0003), TNF-α (4.746 ± 2.4 vs 11.92 ± 1.8; p = 0.047) and IFN-γ (2.714 ± 0.45 vs 4.344 ± 0.4; p = 0.036) and inhibited IL-22 (24.82 ± 4.07 vs 11.01 ± 2.186; p = 0.01) gene expression by liver lymphocytes of recipient mice. NK1.1 cells are major source of IL-22 in islets recipient mice liver and anti-IL-22 antibody treatment of recipient mice reduced allograft survival to 6-9 days compared to 18-21 days in isotype control antibody treated mice. Recombinant IL-22 but not IFN-γ enhanced insulin production by pancreatic islets of BALB/c mice (102.0 ± 22.65 vs 33.41 ± 12.07; p = 0.03) and enhanced expression of genes Reg2, Reg3a and Reg3g involved in islet survival. Further studies indicated that immunization and challenge of type 1 diabetic C57BL/6 mice with TLR9 agonist can enhance IL-22 production by NK1.1 cells and prolongs pancreatic allograft survival from 15 days to 45 days. The sum of our studies suggests that IL-22 produced by liver NK1.1 cells enhance allograft survival and TLR9 agonist can be used to prolong pancreatic allograft survival.