RNA-Binding Motif 3 (RBM3) regulates Type 2 Innate Lymphoid cell (ILC2) Cytokine Production
Type 2 immune responses, such as asthma, occur after exposure to allergens and are characterized by the release of cytokines that include IL4, IL5, IL9, IL10, and IL13 (Spellberg et al. 2000). Until the last decade, these cytokines were thought to be produced by conventional CD4+ Th2 cells only and thus, were identified as Th2 cytokines. However, it was recently discovered that Type 2 Innate Lymphoid cells (ILC2s) also potently produce Th2 cytokines and play a role in Type 2 immune responses. Previous research has also demonstrated that the protein, RNA Binding Motif 3 (RBM3), is one of ten highly expressed genes that contributes to airway hyperresponsiveness in an animal model of asthma. Our preliminary data has revealed that sorted ILC2s from mice challenged with the fungal allergen Alternaria have demonstrated higher expression of RBM3 when compared to PBS challenged controls. Thus, this study serves to determine the role of RBM3 in regulating ILC2 Th2 cytokine production and its contributions to type 2 inflammation. It was originally postulated that RBM3 serves to aide in cytokine production via Th2 cytokine mRNA stability; however, data acquired provides evidence of a different potential relationship between RBM3 and Th2 cytokine production. Utilizing a 7-day Alternaria model, wild-type and RBM3KO mice were challenged with Alternaria to induce asthmatic-like responses. RBM3KO mice expressed higher cell counts and percentages of eosinophils, IL5 expressing ILC2s, and IL13 expressing ILC2s than wild-type controls. In vitro data preliminarily supports that ILC2s lacking RBM3 are more active compared to WT ILC2s. These data suggest that RBM3 may be a negative regulator of ILC2 responses. This work may provide novel avenues for therapeutic approaches to asthma.