Acinar Cells of the Pancreas Are a Target of Interleukin-22

Abstract

Interleukin-22 (IL-22) (also reported as IL-10-related T cell-derived inducible factor, IL-TIF) is a recently identified cytokine found to signal through a receptor comprising the class II cytokine receptor family members IL-10Rbeta/CRF2-4 and IL-22R. Previous work has established that IL-10Rbeta, also a component of the IL10R complex, exhibits a broad distribution of mRNA expression. Here, we observe that IL-22R exhibits a restricted expression pattern, with highest levels of mRNA expression in pancreas and detectable expression in multiple other tissues, particularly liver, small intestine, colon, and kidney. We find that isolated primary pancreatic acinar cells and the acinar cell line 266-6 respond to IL-22 with activation of Stat3 and changes in gene transcription. IL-22 mediates robust induction of mRNA for pancreatitis-associated protein (PAP1)/Reg2 and osteopontin (OPN). PAP1 is a secreted protein related to the Reg family of trophic factors and was initially characterized as a protein elevated in pancreatitis. In vivo injection of IL-22 resulted in rapid induction of PAP1 in pancreas, a response not observed in mice deficient in IL-10Rbeta. These results support the conclusion that IL-10Rbeta is a required common component of both the IL-10 and IL-22 receptors and suggest that IL-22 may play a role in the immune response in pancreas.