Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease?

Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13306-11. doi: 10.1073/pnas.231474098. Epub 2001 Oct 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Autoimmune Diseases / immunology*
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Crohn Disease / etiology
  • Crohn Disease / immunology*
  • DNA Primers
  • Enteric Nervous System / immunology
  • Enteric Nervous System / metabolism
  • Enterocolitis / etiology
  • Enterocolitis / immunology*
  • Female
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Glial Fibrillary Acidic Protein / physiology
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Neuroglia / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / physiology

Substances

  • DNA Primers
  • Glial Fibrillary Acidic Protein
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Antigen, T-Cell