Tumor necrosis factor-receptor 2 is up-regulated on lamina propria T cells in Crohn's disease and promotes experimental colitis in vivo.

Détails

ID Serval
serval:BIB_DCC07516523A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tumor necrosis factor-receptor 2 is up-regulated on lamina propria T cells in Crohn's disease and promotes experimental colitis in vivo.
Périodique
European Journal of Immunology
Auteur(s)
Holtmann M.H., Douni E., Schütz M., Zeller G., Mudter J., Lehr H.A., Gerspach J., Scheurich P., Galle P.R., Kollias G., Neurath M.F.
ISSN
0014-2980 (Print)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2002
Volume
32
Numéro
11
Pages
3142-3151
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Tumor necrosis factor (TNF) plays a pivotal role in the pathogenesis of Crohn's disease (CD). However, little is known about the role of TNF receptors (TNF-R) in this disease. Here, we found that TNF-R2 (in contrast to TNF-R1) was significantly up-regulated on lamina propria and peripheral blood T cells in CD compared to control patients. To directly test the functional role of TNF-R2 in Th1-mediated experimental colitis in vivo, we took advantage of transgenic animals overexpressing TNF-R2 in T cells. Reconstitution of SCID mice with CD4+ CD62L+ T cells from TNF-R2 transgenic mice led to an earlier wasting syndrome, a more severe colitis and augmented Th1 cytokine production than reconstitution with cells from wild-type littermates. In addition, TUNEL staining revealed a significantly decreased apoptosis rate of lamina propria mononuclear cells in mice reconstituted with TNF-R2 transgenic T cells compared to mice reconstituted with wild-type T cells. In summary, our data suggest a critical regulatory role of TNF-R2 signaling for disease exacerbation in Th1-mediated chronic colitis. Taken together with the increased expression of TNF-R2 in CD, selective targeting of TNF-R2 signaling thus emerges as a potentially novel approach to the treatment of CD.
Mots-clé
Adult, Animals, Antigens, CD/biosynthesis, Antigens, CD/physiology, Apoptosis, Chronic Disease, Colitis/immunology, Colon/immunology, Crohn Disease/etiology, Crohn Disease/immunology, Female, Humans, Interferon-gamma/biosynthesis, Interleukin-4/biosynthesis, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, SCID, Mice, Transgenic, Middle Aged, Receptors, Tumor Necrosis Factor/biosynthesis, Receptors, Tumor Necrosis Factor/physiology, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, T-Lymphocytes/metabolism, Up-Regulation
Pubmed
Open Access
Oui
Création de la notice
26/11/2011 14:01
Dernière modification de la notice
20/08/2019 16:01
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