IL-22 producing NK cells aid in the repair of damaged tissues (INC5P.326)

Abstract

Abstract Natural killer (NK) cells are lymphocytes of the innate immune system that are associated with killing of virally infected and neoplastic cells. They have been shown to produce large amounts of pro-inflammatory cytokines, such as IFN-γ, and cytotoxic molecules, such as perforin and granzyme. Recent studies have identified unique subsets of natural killer cells, with distinct effector functions not limited to their classic cytotoxic function. These functions include producing a new array of cytokines, including IL-22, which has been shown to aid in tissue regeneration. Here, we provide evidence for a NK cell subset with the capacity to aid in the repair of tissue damage following viral infection as well as radiation damage. Using an in vitro co-culture system where we culture unstimulated NK cells with virally infected fibroblasts or irradiated epithelial cells, we were able to identify triggers that induce the expression of IL-22. In order to test the biological significance of IL-22 production by NK cells, we next used an in vivo murine cytomegalovirus (MCMV) model where we are able to deplete or adoptively transfer the IL-22 producing subset. With this model we are able show differences in liver pathology following MCMV infection, dependent on an IL-22 producing NK cell subset. A better understanding of IL-22 production by natural killer cells, and delineating a specific IL-22 producing subset could offer therapeutic benefits to patients who receive radiation therapy.