Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Gastroenterology. 2012 Apr;142(4):865-874.e2. doi: 10.1053/j.gastro.2011.12.036. Epub 2011 Dec 24.

The membrane-bound mucin Muc1 regulates T helper 17-cell responses and colitis in mice.

Author information

  • 1Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.

Abstract

BACKGROUND & AIMS:

T helper (Th) 17 cells produce the effector cytokine interleukin (IL)-17, along with IL-22, which stimulates colonic epithelial cells to produce a membrane-bound mucin, Muc1. Muc1 is a component of the colonic mucus, which functions as a lubricant and a physiologic barrier between luminal contents and mucosal surface. The gene MUC1 has been associated with susceptibility to inflammatory bowel disease; we investigated the role of Muc1 in development of colitis in mice.

METHODS:

Muc1 and RAG1 were disrupted in mice (Muc/RAG double knockout mice); Th1-mediated colitis was induced by intravenous injection of CD4(+)CD45RB(high) T cells. We also studied Th2-mediated colitis using mice with disruptions in Muc1 and T-cell receptor α chain (Muc/TCR double knockout mice).

RESULTS:

Muc1 deficiency led to the development of more severe forms of Th1- and Th2-induced colitis than controls. Loss of Muc1 increased colonic permeability and the Th17-cell, but not Th2 or Th1 cell, response in the inflamed colon. Loss of Muc1 also promoted expansion of an innate lymphoid cell population (Lin(-) ckit(-) Thy1(+) Sca1(+)) that produces IL-17. The expansion of Th17 adaptive immune cells and innate lymphoid cells required the commensal microbiota.

CONCLUSIONS:

Muc1, which is up-regulated by Th17 signaling, functions in a negative feedback pathway that prevents an excessive Th17 cell response in inflamed colons of mice. Disruption of this negative feedback pathway, perhaps by variants in Muc1, might contribute to inflammatory bowel disease in patients.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
22202458
[PubMed - indexed for MEDLINE]
PMCID:
PMC3441148
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk