More than a decoy receptor? Interleukin 22 Binding Protein (IL-22BP) in bacterial pneumonia

Abstract

Abstract IL-22 is secreted by lymphoid cells such as Th17 cells and ILC3s. The IL-22 receptor is composed of IL-22Ra1 and IL-10Rbeta. In the lung, the IL-22R localizes in the upper airway epithelial cells. We previously reported that IL-22 contains pneumococcal lung infection due to hepatic activation of C3 and improved cellular phagocytosis. IL-22 also binds to a natural antagonist, known as IL-22BP or IL-22Ra2. In vitro, IL-22BP binds to IL-22 with high affinity, competing with IL-22R and neutralizing IL-22 activity. Studies have shown that IL-22BP controls tumor development in the colon, regulates inflammation in autoimmune encephalitis and promotes bacterial uptake in Peyer’s patches. However, it is unclear whether these multifaceted effects associated with IL-22BP are due solely to IL-22 binding and neutralization, given discrepant phenotypes in IL-22−/− versus IL-22BP−/− mice. Furthermore, surprisingly little is known about IL-22BP in the lung. We therefore interrogated the role of IL-22BP in a mouse model of bacterial pneumonia. In naïve lungs, we saw that IL-22BP is mostly expressed in alveolar and airway epithelial cells. IL-22BP−/− mice were less susceptible than controls to Streptococcus pneumoniae infection. This resistance was not due to differences in cellular recruitment, neutrophil phagocytosis or chemokine expression. RNA-Seq analyses of total lung tissue that compared infected IL-22BP−/− cohorts versus wild type revealed differential expression of several genes in the mitochondrial oxidative phosphorylation pathway. These data were strikingly different from prior findings made in IL-22−/−mice, leading us to speculate that IL-22BP may regulate mitochondria metabolism and have functions beyond the IL-22 system.