Department of Gastroenterology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Eur J Immunol. 2021 Feb;51(2):459-470. doi: 10.1002/eji.202048622. Epub 2020 Nov 16.
Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)-specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag-specific IgG amounts in colon biopsies of UC patients. UC patient-derived Ag-specific PMNs could be activated upon exposure to food specific Ag. The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re-exposure of sensitized PMNs to specific Ag triggered PMN activation and induced UC-like inflammation in the mouse colon. We conclude that FcγRI plays a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC.
溃疡性结肠炎（UC）是一种经常复发的疾病，影响超过 0.1%的普通人群；其潜在机制尚未完全了解。已发表的数据表明，多形核粒细胞（PMN）有助于 UC 的发病机制。本研究旨在鉴定抗原（Ag）特异性 PMN，并研究其在 UC 复发中的作用。在本研究中，评估了一组 UC 患者中 PMN 活性与 UC 复发之间的相关性。建立了 UC 小鼠模型以扩展 UC 患者研究的结果。结果表明，UC 患者结肠活检中 PMN 活性与食物特异性 IgG 量之间存在正相关。UC 患者来源的 Ag 特异性 PMN 可在暴露于食物特异性 Ag 时被激活。在 UC 患者的 PMN 表面检测到 Ag/FcγRI 复合物。致敏的 PMN 再次暴露于特异性 Ag 会触发 PMN 激活，并在小鼠结肠中诱导 UC 样炎症。我们得出结论，FcγRI 在 UC 复发中起关键作用。抑制 FcγRI 可有效抑制实验性 UC。
