UC San Diego

Although asthma has been classically understood as being type 2 T helper cell (Th2) cell driven, a new player has entered the arena of asthmatic response. Group 2 innate lymphoid cells (ILC2s) are recently discovered and have been shown to mediate the innate inflammatory features of asthma. ILC2s produce the same cytokines and rely on the same transcription factors that Th2 cells do but lack the lineage markers associated with other immune cells. Alternaria alternata is a fungal protease allergen associated with asthma that has been shown to induce a powerful release of IL33 and therefore, induce a strong ILC2-mediated eosinophilic lung inflammatory response. However, we have found that if Alternaria is combined with c-di-GMP during intranasal challenges in wild type mice, the eosinophilic lung response associated with asthma is severely attenuated. Importantly, we have found that this attenuation of type 2 inflammation by c-di-GMP is completely prevented in STINGKO mice. Thus, we have identified a completely novel pathway to reduce innate ILC2-driven type 2 inflammation induced by the clinically-relevant allergen Alternaria.