Enterocolitis Induced by Autoimmune Targeting of Enteric Glial Cells: a Possible Mechanism in Crohn's Disease?

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Nov 1

PMID 11687633

Citations 124

Authors

A Cornet

T C Savidge

J Cabarrocas

W L Deng

J F Colombel

H Lassmann

P Desreumaux

R S Liblau

Affiliations

Soon will be listed here.

Abstract

Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8(+) T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

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