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Persistent gut motor dysfunction in a murine model of T‐cell‐induced enteropathy
Author(s) -
Mizutani T.,
Akiho H.,
Khan W. I.,
Murao H.,
Ogino H.,
Kanayama K.,
Nakamura K.,
Takayanagi R.
Publication year - 2010
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2009.01396.x
Subject(s) - medicine , endocrinology , enteropathy , antibody , small intestine , irritable bowel syndrome , t cell , cd3 , immune system , immunology , cd8 , disease
Background Inflammatory bowel disease (IBD) patients in remission often experience irritable bowel syndrome (IBS)‐like symptoms. We investigated the mechanism for intestinal muscle hypercontractility seen in T‐cell‐induced enteropathy in recovery phase. Methods BALB/c mice were treated with an anti‐CD3 antibody (100 μg per mouse) and euthanized at varying days post‐treatment to investigate the histological changes, longitudinal smooth muscle cell contraction, cytokines (Th1, Th2 cytokines, TNF‐α) and serotonin (5‐HT)‐expressing enterochromaffin cell numbers in the small intestine. The role of 5‐HT in anti‐CD3 antibody‐induced intestinal muscle function in recovery phase was assessed by inhibiting 5‐HT synthesis using 4‐chloro‐DL‐phenylalanine (PCPA). Key Results Small intestinal tissue damage was observed from 24 h after the anti‐CD3 antibody injection, but had resolved by day 5. Carbachol‐induced smooth muscle cell contractility was significantly increased from 4 h after injection, and this muscle hypercontractility was evident in recovery phase (at day 7). Th2 cytokines (IL‐4, IL‐13) were significantly increased from 4 h to day 7. 5‐HT‐expressing cells in the intestine were increased from day 1 to day 7. The 5‐HT synthesis inhibitor PCPA decreased the anti‐CD3 antibody‐induced muscle hypercontractility in recovery phase. Conclusions & Inferences Intestinal muscle hypercontractility in remission is maintained at the smooth muscle cell level. Th2 cytokines and 5‐HT in the small intestine contribute to the maintenance of the altered muscle function in recovery phase.