Interleukin (IL)-23 Mediates Toxoplasma Gondii-induced Immunopathology in the Gut Via Matrixmetalloproteinase-2 and IL-22 but Independent of IL-17

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2009 Dec 10

PMID 19995958

Citations 151

Authors

Melba Munoz

Markus M Heimesaat

Kerstin Danker

Daniela Struck

Uwe Lohmann

Rita Plickert

Stefan Bereswill

Andre Fischer

Ildiko Rita Dunay

Kerstin Wolk

Christoph Loddenkemper

Hans-Willi Krell

Claude Libert

Leif R Lund

Oliver Frey

Christoph Holscher

Yoichiro Iwakura

Nico Ghilardi

Wenjun Ouyang

Thomas Kamradt

Robert Sabat

Oliver Liesenfeld

Affiliations

Soon will be listed here.

Abstract

Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23-mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii-induced immunopathology. Moreover, IL-23-dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down-regulated and dispensable. CD4(+) T cells were the main source of IL-22 in the small intestinal lamina propria. Thus, IL-23 regulates small intestinal inflammation via IL-22 but independent of IL-17. Gelatinases may be useful targets for treatment of intestinal inflammation.

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