Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa

J Crohns Colitis. 2021 Sep 25;15(9):1491-1499. doi: 10.1093/ecco-jcc/jjab041.

Abstract

Background and aims: Pouchitis is a common complication following formation of an ileal pouch-anal anastomosis [IPAA] after proctocolectomy for ulcerative colitis [UC]. Gut-specific lymphocyte trafficking mechanisms have been identified as players in the pathogenesis of UC. In the present study, we aimed to characterise the presence of lymphocyte subsets expressing gut-homing molecules in pouches and peripheral blood of UC patients with and without pouchitis.

Methods: Biopsy samples and peripheral blood were collected from 29 patients with an IPAA [seven with active inflammation, 22 without inflammation]. Expression of adhesion molecule MAdCAM-1 was assessed using immunohistochemistry, and flow cytometry was used to characterise expression of integrin α4β7, C-chemokine receptor 9 [CCR9], and CD103 on T cell subsets.

Results: MAdCAM-1 expression was significantly increased in case of active inflammation in the pouch. T cells expressing integrin α4β7 were abundant in the pouch mucosa, but the frequency of integrin α4β7-expressing T cells was decreased on CD4+ lymphocytes during inflammation. Co-expression of gut-homing markers CCR9 and α4β7 was more pronounced in biopsies compared with peripheral blood, but was not enhanced upon active inflammation.

Conclusions: Gut-homing T cells are abundant in pouch mucosa, but the classic hypothesis that the chronic inflammatory state is maintained by an accumulation of α4β7-expressing effector T cells is not supported by our data.

Keywords: MAdCAM-1; Pouchitis; integrin alpha4beta7.

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Case-Control Studies
  • Cell Adhesion Molecules / metabolism*
  • Cohort Studies
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / surgery*
  • Female
  • Humans
  • Integrin alpha Chains / metabolism
  • Integrins / metabolism*
  • Male
  • Middle Aged
  • Mucoproteins / metabolism*
  • Pouchitis / etiology
  • Pouchitis / metabolism*
  • Proctocolectomy, Restorative / adverse effects*
  • Receptors, CCR / metabolism
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, CD
  • CC chemokine receptor 9
  • Cell Adhesion Molecules
  • Integrin alpha Chains
  • Integrins
  • MADCAM1 protein, human
  • Mucoproteins
  • Receptors, CCR
  • alpha E integrins
  • integrin alpha4beta7