Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease?
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.
Cornet
A
A
Institut National de la Santé et de la Recherche Médicale U546 and Immunology Laboratory, Pitié-Salpêtrière Hospital, Paris 75013, France.
Savidge
T C
TC
Cabarrocas
J
J
Deng
W L
WL
Colombel
J F
JF
Lassmann
H
H
Desreumaux
P
P
Liblau
R S
RS
D000293:Adolescent; D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000209:etiology / Q000276:immunology*; D017931:DNA Primers; D017615:Enteric Nervous System / Q000276:immunology / Q000378:metabolism; D004760:Enterocolitis / Q000209:etiology / Q000276:immunology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009457:Neuroglia / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology
D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011948:Receptors, Antigen, T-Cell