‘The role of phagocytic NADPH oxidase and innate immune cells in the immune activation in toluene diisocyanate (TDI)-induced lung inflammation’

Abstract

Abstract Innate lymphoid cells (ILCs) have been known to play an important role in development of lymphoid tissues and in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. Isocyanates are low-molecular-weight compounds noted for inducing an oxidant stress-dependent pulmonary inflammation, which is the leading cause of occupational asthma. Our previous studies indicated that phagocytic NADPH oxidase is an essential regulator in TDI-induced airway inflammation characterized by a server lung inflammation with both Th17 and Th2 immune components. In this study, we hypothesized that ILCs activation may play an important role in phagocytic NADPH oxidase-mediated downstream immune mechanism in TDI-induced airway inflammation. The wild type (WT) and phagocytic NADPH oxidase deficient (Ncf1−/−) mice were sensitized and challenged with 3% TDI to induce lung inflammation. Our results showed that type 2 inflammatory cytokines, including IL-33 and IL-5, increased in both WT and Ncf1−/−mice but more significantly in TDI-induced lung inflammation. Moreover, the pro-inflammatory cytokine IL-1b and IL-17A production was only induced by TDI-exposure in WT but not in Ncf1−/− mice. We also found that the population of lineage negative and CD45 positive cells was identified in inflammation lung tissue. Comparison of ILCs population between TDI-induced WT mice and Ncf1−/− mice showed that the number of ILC2s and ILC3s were significantly higher in WT mice. These results suggested that ROS may modulate the activation of ILC2s, ILC3s and may determine the Th2 and Th17 cytokines production in the TDI-induced lung inflammation.