Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens.

Détails

ID Serval
serval:BIB_40A32C7709BB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens.
Périodique
Journal of Immunology
Auteur(s)
Wirtz S., Finotto S., Kanzler S., Lohse A.W., Blessing M., Lehr H.A., Galle P.R., Neurath M.F.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
1999
Volume
162
Numéro
4
Pages
1884-1888
Langue
anglais
Résumé
We generated transgenic mice for STAT-4, a regulatory protein specifically associated with IL-12 signaling, under the control of a CMV promoter. These mice expressed strikingly increased nuclear STAT-4 levels in lamina propria CD4+ T lymphocytes upon systemic administration of dinitrophenyl-keyhole limpet hemocyanin and developed chronic transmural colitis characterized by infiltrates of mainly CD4+ T lymphocytes. The latter cells produced predominantly TNF and IFN-gamma but not IL-4 upon activation with alphaCD3/CD28 or autologous bacterial Ags, consistent with a Th1-type cell response. Furthermore, chronic colitis in STAT-4 transgenic mice could be adoptively transferred to SCID mice by colonic and splenic CD4+ T cells that were activated with Ags from autologous bacterial flora. These data establish a critical molecular signaling pathway involving STAT-4 for the pathogenesis of chronic intestinal inflammation, and targeting of this pathway may be relevant for the treatment of colitis in humans.
Mots-clé
Adoptive Transfer/methods, Animals, Antigens, Bacterial/immunology, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/metabolism, Chronic Disease, Colitis/genetics, Colitis/immunology, Crosses, Genetic, Cytokines/biosynthesis, DNA-Binding Proteins/biosynthesis, DNA-Binding Proteins/genetics, Haptens/immunology, Hemocyanin/immunology, Interferon-gamma/biosynthesis, Intestinal Mucosa/metabolism, Intestinal Mucosa/microbiology, Lymphocyte Activation/immunology, Mice, Mice, Inbred Strains, Mice, SCID, Mice, Transgenic, STAT4 Transcription Factor, Signal Transduction/genetics, Signal Transduction/immunology, Trans-Activators/biosynthesis, Trans-Activators/genetics, Tumor Necrosis Factor-alpha/biosynthesis
Pubmed
Création de la notice
25/11/2011 20:44
Dernière modification de la notice
03/03/2018 16:29
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