STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING^-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING^-/- mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING^-/- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.

中文翻译：

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细胞溶质传感器 STING 是肠道稳态和炎症控制所必需的。

STING（干扰素基因刺激剂）是环状二核苷酸的胞质传感器，也是细胞内 DNA 受体的衔接分子。尽管 STING 在宿主防御病原体和自身免疫性疾病中具有重要功能，但其在肠道稳态中的生理相关性在很大程度上是未知的。在这项研究中，我们发现与野生型 (WT) 小鼠相比，STING ^-/-小鼠的肠粘膜保护机制存在缺陷，包括杯状细胞数量减少、粘液产生减少和分泌性 IgA 水平降低。粪便含量和微生物群 DNA 可以激活 STING，表明该分子在肠道中的作用。STING 中的微生物群组成发生了变化^-/-小鼠趋向于更炎症的特征，证明异杆菌属和双歧杆菌群的减少以及双硫弧菌的增加。STING 的缺失导致诱导上皮内淋巴细胞 (IEL) 减少，第 1 组先天性淋巴细胞 (ILC1) 和 ILC3 频率增加，结肠中 ILC2 减少。Foxp3+ 和 LAP+ 调节性 T 细胞的发育和功能在 STING ^-/-小鼠中也受到损害。此外，与 WT 动物相比，这些小鼠对葡聚糖硫酸钠诱导的结肠炎、T 细胞诱导的结肠炎和肠道鼠伤寒沙门氏菌感染高度敏感。因此，我们的结果确定了 STING 在维持肠道稳态中的重要作用以及在控制肠道炎症方面的保护作用。