Cyclic-di-GMP Induces STING-Dependent ILC2 to ILC1 Shift During Innate Type 2 Lung Inflammation

Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group innate lymphoid cells (ILC2s) are critical drivers type lung during fungal allergen exposure mice; however, it unclear how CDG regulates ILC responses inflammation. Here, we show that intranasal induced early airway 1 interferon (IFN) production dramatically suppressed CD127+ST2+ ILC2s Alternaria IL-33 exposure. Further, CD127–ST2–Thy1.2+ ILCs, showed a transcriptomic signature consistent ILC1s, were expanded activated by combined either or IL-33. CDG-mediated suppression occurred independent IL-18R, IL-12, STAT6 but required stimulator genes (STING) IFN signaling. Thus, potently suppresses ILC2-driven promotes ILC1 responses. results suggest potential therapeutic modulation STING to suppress and/or increase anti-viral respiratory infections.