FcγRI plays a critical role in patients with ulcerative colitis relapse

Eur J Immunol. 2021 Feb;51(2):459-470. doi: 10.1002/eji.202048622. Epub 2020 Nov 16.

Abstract

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.

Keywords: FcγRI; Immunity; Intestine; PMN; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology*
  • Colon / metabolism
  • Colon / pathology
  • Female
  • Humans
  • Immunoglobulin G / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Activation / physiology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Reactive Oxygen Species / metabolism
  • Receptors, IgG / metabolism*
  • Recurrence

Substances

  • Immunoglobulin G
  • Reactive Oxygen Species
  • Receptors, IgG