Gene expression response to silica treatment in wild-type C57 black 6 mice vs Rag1 knockout, NK-depleted mice

The lung is constantly exposed to potentially pathogenic particles and microorganisms. It has recently become evident that not only innate, but also adaptive immune responses to particulates such as crystalline silica (SiO2) entering the respiratory tract are complex and dynamic events. Although the cellular mechanisms and anatomical consequences involved in the development of silicosis have been extensively studied, they still remain poorly understood. Based on their capacity for immune regulation, lymphocytes may play a role in determining the respiratory response to environmental challenge by SiO2. The objective of this study was to characterize the impact of SiO2 exposure on respiratory immune processes, with particular emphasis on evaluating the importance of lymphocytes in the murine silicosis model. Therefore, we utilized lymphopenic mice including NK deficient, Rag1-/- or a combination (Rag1-/- NK depleted) and demonstrated that SiO2-induced fibrosis and inflammation occur independently of T, B, NK T, and NK cells. Studies in Rag1-/- mice further suggest that lymphocytes may participate in controlling SiO2-induced inflammation through modulation of the Nalp3 inflammasome. This observation may have clinical relevance in the treatment of inflammatory and fibrotic lung diseases that are either refractory or respond sub-optimally to current therapeutics. 2 replicates each of WT C57Bl6 saline treated, WT C57Bl6 silica treated, RagKO saline treated and RagKO silica treated.