‘The role of leukocyte NADPH oxidase in the regulation of IL-1 family cytokines and innate lymphoid cells in serum-induced arthritis.’

Abstract

Abstract Innate lymphoid cells (ILCs) have been recently identified in different tissues as an important class of innate immune cells involved in the inflammatory response during health and disease. Our previous studies showed that reactive oxygen species (ROS) act as negative feedback to regulate IL-1β-mediated inflammation, accounting for the more severe arthritis in the absence of leukocyte NADPH oxidase (NOX2), which is responsible for producing most of the ROS in inflammatory tissues. In this study, we set out to identify and characterize innate lymphoid cells in the arthritic joints based on the hypothesis that leukocyte-produced ROS are critical for modulating innate lymphoid cells activation and IL-1 family cytokines production in serum induced arthritis. We found that serum-induced joint inflammation may be more severe and induce higher IL-1β, IL-18 but less IL-33 cytokines expression and a population of lineage-negative CD45 positive cells was identified in the synovial fluid and tissue of diseased joints. Comparison of ILC populations between WT and Ncf1−/− arthritic mice showed that ILC2 and NCR posetive ILC3 were more abundant in the joint of NOX2 deficient mice. Moreover, the phagocytic NADPH oxidase was an essential regulator of ILC3 populations switching in the inflammatory tissues of arthritis. Given the fact that these cells are capable of rapid cytokine production and leukocyte-produced ROS appear to affect these ILC populations, our ongoing investigations promise to reveal novel redox-sensitive immunoregulatory mechanisms mediated by ILC through IL-1 family cytokines.