Crossover subsets of CD4(+) T lymphocytes in the intestinal lamina propria of patients with Crohn's disease and ulcerative colitis

Research output: Contribution to journalArticle

Authors

  • Ji Li
  • Aito Ueno
  • Miriam Fort Gasia
  • Humberto B Jijon
  • Remo Panaccione
  • Gilaad G Kaplan
  • Paul L Beck
  • Joanne Luider
  • Herman W Barkema
  • Jiaming Qian
  • Xianyong Gui

Colleges, School and Institutes

External organisations

  • Gastrointestinal Research Group/Department of Medicine, HSC1838, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada.
  • Calgary Laboratory Services, Calgary, AB, Canada.
  • Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China.
  • Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada.

Abstract

Background
Hovhannisyan et al. first showed evidence of plasticity between Treg and Th17 in the inflamed intestine of Crohn’s disease (CD) patients. Our previous report suggests that the inflammatory cytokine milieu generates IL-17+ Foxp3+ CD4+ T lymphocytes which is a crossover population converting Treg subset to Th17 in the peripheral blood of IBD patients. This is considered as an evidence of Treg/Th17 plasticity.

Aim
The aim of this study was to characterize a variety of helper T cell crossover population, not limited to IL-17+ Foxp3+ CD4+ T lymphocytes, in the lamina propria (LP) of IBD patients.

Methods
Fresh colonoscopic biopsies were obtained from patients with CD (n = 50) and ulcerative colitis (UC, n = 32) and from healthy controls (HC, n = 25). LP mononuclear cells were assessed for intracellular cytokines and transcription factors such as IFNγ, IL-13, IL-17, IL-22, T-bet, Gata-3, RORγt, and Foxp3 using multicolor flow cytometry to detect subsets of LP CD4+ T lymphocytes.

Results
Patients with IBD demonstrated increased crossover populations in IL-17+ Foxp3+, T-bet+ Foxp3+, Gata3+ Foxp3+, RORγt+ Foxp3+ populations compared to HC. There was an inverse correlation of Harvey–Bradshaw index with Gata3+ Foxp3+ population in CD patients, while IL-13+ Foxp3+ population was directly correlated with Mayo clinical scores in UC patients. Furthermore, total IL-22 expressing cells as well as Th22 and IL-22+ Th1 populations were decreased in UC compared to CD and HC.

Conclusion
IBD patients exhibit the increased crossover populations in LP Treg cells toward Th2 and Th17 compared to HC. The prevalence of Treg/Th2 crossover populations is associated with clinical disease score of IBD.

Details

Original languageEnglish
Pages (from-to)2357-2368
JournalDigestive Diseases and Sciences
Volume62
Early online date1 Jun 2017
Publication statusE-pub ahead of print - 1 Jun 2017

Keywords

  • Journal Article, T cell crossover population , Crohn's disease , ulcerative colitis , regulatory T cells , Th17 , Th22