Department of Biomedicine, Gastroenterology, University of Basel, 4031, Basel, Switzerland.
Swiss Institute of Bioinformatics, 4031, Basel, Switzerland.
Mucosal Immunol. 2022 Mar;15(3):443-458. doi: 10.1038/s41385-022-00494-y. Epub 2022 Mar 9.
Goblet cells secrete mucin to create a protective mucus layer against invasive bacterial infection and are therefore essential for maintaining intestinal health. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. In this study, we show that epithelial Gpr35 plays a critical role in goblet cell function. In mice, cell-type-specific deletion of Gpr35 in epithelial cells but not in macrophages results in goblet cell depletion and dysbiosis, rendering these animals more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows that the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota.
杯状细胞分泌粘蛋白，形成保护性黏液层，抵御侵袭性细菌感染，因此对维持肠道健康至关重要。然而，调节杯状细胞功能的分子途径在很大程度上仍不清楚。虽然 GPR35 在结肠上皮细胞中高度表达，但它在促进上皮屏障中的重要性尚不清楚。在这项研究中，我们表明上皮细胞中的 Gpr35 在杯状细胞功能中起着关键作用。在小鼠中，上皮细胞而非巨噬细胞中特异性敲除 Gpr35 会导致杯状细胞耗竭和菌群失调，使这些动物更容易感染柠檬酸杆菌。从机制上讲，单细胞 RNA 测序分析表明，上皮细胞 Gpr35 的信号对于维持杯状细胞中正常的细胞焦亡水平是必不可少的。我们的工作表明，上皮细胞中 Gpr35 的存在是杯状细胞介导的宿主与微生物群共生的关键因素。
