Background Trefoil factor family cytokines (TFF1-3) have documented reparative and immunoregulatory effects on mucosal epithelial cells that include: blocking apoptosis, directed cell migration, and regulation of pro-inflammatory cytokine production. TFF1 and TFF3 have been shown to undergo altered expression within sinonasal tissues of patients with various forms of chronic rhinosinusitis including those with or wthout polyp associated disease, but the cellular source(s) of TFF members in CRS remains unclear. To further explore the role of TFF3 in inflammatory sinonasal disease, we sought to determine its expression pattern in immune and non-immune cell types in CRS disease. Methods Polyp and inferior turbinate tissues were isolated from patients undergoing surgical resection for treatment of CRS. Tissue homogenates and single cell suspensions were subjected to enzyme linked immunosorbent assay (ELISA) and single-cell RNA sequencing. Air liquid interface cultures of sinonasal epithelia were subjected to immunofluorescence (IF) microscopy. Interleukin 25, TFF2 and TFF3 protein levels were compared to sinonasal outcome test scores (SNOT-22) to determine whether levels associated with post-operative outcomes. Results TFF3 was broadly expressed in goblet cells, ciliated cells, Tuft cells and T lymphocytes. TFF3 protein levels positively associated with IL-25 in CRSwNP patients. Lastly, TFF3 protein levels positively associated with clinical improvement post-surgery. Conclusions TFF3 is broadly expressed within multiple epithelial and immune cell lineages in patients with CRSwNP. Protein levels of TFF3 correlate with IL-25 and clinical signs of disease, however TFF3 levels associate with clinical improvement following surgical intervention indicating a potential beneficial role for this reparative cytokine in CRS patients.

中文翻译：

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三叶因子3与慢性鼻鼻窦炎患者的IL-25呈正相关

背景技术三叶因子家族细胞因子（TFF1-3）已记录了对粘膜上皮细胞的修复和免疫调节作用，包括：阻断细胞凋亡，定向细胞迁移以及调节促炎性细胞因子的产生。已经显示出TFF1和TFF3在患有各种形式的慢性鼻-鼻窦炎的患者，包括患有或没有息肉相关疾病的慢性鼻-鼻窦炎患者的鼻窦组织中发生改变的表达，但是CRS中TFF成员的细胞来源仍然不清楚。为了进一步探讨TFF3在炎性鼻窦疾病中的作用，我们试图确定其在CRS疾病的免疫和非免疫细胞类型中的表达模式。方法从接受手术切除的CRS患者中分离出息肉和下鼻甲组织。对组织匀浆和单细胞悬液进行酶联免疫吸附测定（ELISA）和单细胞RNA测序。对鼻窦上皮的气液界面培养物进行免疫荧光（IF）显微镜检查。将白细胞介素25，TFF2和TFF3蛋白水平与鼻腔鼻窦预后评分（SNOT-22）进行比较，以确定水平是否与术后预后相关。结果TFF3在杯状细胞，纤毛细胞，塔夫特细胞和T淋巴细胞中广泛表达。在CRSwNP患者中，TFF3蛋白水平与IL-25呈正相关。最后，TFF3蛋白水平与手术后的临床改善呈正相关。结论TFF3在CRSwNP患者的多种上皮细胞和免疫细胞谱系中广泛表达。