Veterinärmedizinische Universität Wien Forschungsinformationssystem VetDoc

Grafischer Link zur Startseite der Vetmeduni Vienna

Gewählte Publikation:

Open Access Logo

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2015

AutorInnen: Hainzl, E; Stockinger, S; Rauch, I; Heider, S; Berry, D; Lassnig, C; Schwab, C; Rosebrock, F; Milinovich, G; Schlederer, M; Wagner, M; Schleper, C; Loy, A; Urich, T; Kenner, L; Han, X; Decker, T; Strobl, B; Müller, M

Titel: Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis.

Quelle: J Immunol. 2015; 195(10):5011-5024



Autor/innen der Vetmeduni Vienna:

Hainzl Eva
Kenner Lukas
Lassnig Caroline
Müller Mathias
Stockinger Silvia
Strobl Birgit

Beteiligte Vetmed-Organisationseinheiten
Institut für Pathologie, Abteilung für Labortierpathologie
Institut für Tierzucht und Genetik, Abteilung für Molekulare Genetik


Zugehörige(s) Projekt(e): Jak Stat - Signalling from Basis to Disease


Abstract:
In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice. Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3.

Keywords Pubmed: Animals
Citrobacter rodentium/immunology
Colitis/genetics
Colitis/immunology*
Colitis/pathology
Enterobacteriaceae Infections/genetics
Enterobacteriaceae Infections/immunology
Enterobacteriaceae Infections/pathology
Interleukins/genetics
Interleukins/immunology*
Intestinal Mucosa/immunology*
Intestinal Mucosa/pathology
Job Syndrome/genetics
Job Syndrome/immunology
Job Syndrome/pathology
Mice
Mice, Knockout
STAT3 Transcription Factor/genetics
STAT3 Transcription Factor/immunology
Signal Transduction/genetics
Signal Transduction/immunology*
TYK2 Kinase/deficiency
TYK2 Kinase/genetics
TYK2 Kinase/immunology*


© Veterinärmedizinische Universität Wien Hilfe und DownloadsErklärung zur Barrierefreiheit