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 of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed both lung proliferating CD127+ST2+ ILC2s and Alternaria- and IL-33-induced lung inflammation. Further, transcriptomic analysis of CD127−ST2−Thy1.2+ ILCs, which were expanded and activated by CDG, revealed an ILC1 signature. CDG administration led to accumulation of IFNγ+ and T-bet+ ILC1s, as well as neutrophilia, independent of IL-18R, IL-12, and STAT6 but dependent on stimulator of interferon genes (STING) and partially dependent on type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.

中文翻译：

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在先天性2型肺部炎症过程中，Cycli-di-GMP诱导STING依赖性ILC2向ILC1转移

在大多数形式的哮喘中发现2型炎症，可能与病毒复发，细菌定植和宿主细胞死亡并存。这些过程驱动细胞内环二核苷酸，例如环二GMP（CDG）的积累。第2组先天淋巴样细胞（ILC2）是小鼠真菌过敏原暴露期间2型肺部炎症的关键驱动因素；但是，尚不清楚CDG在肺部炎症过程中如何调节肺部ILC反应。在这里，我们显示CDG诱导了早期气道1型干扰素（IFN）的产生，并显着抑制了肺增殖CD127 + ST2 + ILC2s和交链孢菌和IL-33引起的肺部炎症。此外，通过CDG扩展和激活的CD127-ST2-Thy1.2 + ILC的转录组学分析揭示了ILC1签名。CDG给药导致IFNγ+和T-bet + ILC1s以及嗜中性粒细胞的积累，独立于IL-18R，IL-12和STAT6，但依赖于干扰素基因的刺激物（STING），部分依赖于1型IFN信号传导。因此，CDG可有效抑制ILC2驱动的肺部炎症并促进ILC1反应。这些结果表明，STING的潜在治疗性调节可抑制2型炎症和/或增加呼吸道感染期间的抗病毒反应。