The Possible Pathogenic Role of IgG4-Producing Plasmablasts in Stricturing Crohn's Disease

Omar Bushara, David Joseph Escobar, Samuel Edward Weinberg, Leyu Sun, Jie Liao, Guang Yu Yang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Background: Crohn's disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. Summary: Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalPathobiology
Volume89
Issue number4
DOIs
StatePublished - Jul 1 2022

Keywords

  • Crohn's disease
  • IgG4-related disease
  • Strictures

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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