TY - JOUR
T1 - Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa
AU - de Krijger, Manon
AU - Wildenberg, Manon E.
AU - Mookhoek, Aart
AU - Verheul, Sascha
AU - de Jonge, Wouter J.
AU - Ponsioen, Cyriel Y.
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
KW - MAdCAM-1
KW - Pouchitis
KW - integrin alpha4beta7
UR - http://www.scopus.com/inward/record.url?scp=85117175599&partnerID=8YFLogxK
U2 - 10.1093/ecco-jcc/jjab041
DO - 10.1093/ecco-jcc/jjab041
M3 - Article
C2 - 33675360
SN - 1873-9946
VL - 15
SP - 1491
EP - 1499
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 9
ER -