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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Authors | Melba Muñoz, Markus M Heimesaat, Kerstin Danker, Daniela Struck, Uwe Lohmann, Rita Plickert, Stefan Bereswill, André Fischer, Ildikò Rita Dunay, Kerstin Wolk, Christoph Loddenkemper, Hans-Willi Krell, Claude Libert, Leif R Lund, Oliver Frey, Christoph Hölscher, Yoichiro Iwakura, Nico Ghilardi, Wenjun Ouyang, Thomas Kamradt, Robert Sabat, Oliver Liesenfeld |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 206
Issue 13
Pg. 3047-59
(Dec 21 2009)
ISSN: 1540-9538 [Electronic] United States |
PMID | 19995958
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukin-17
- Interleukin-23
- Interleukins
- Piperazines
- Pyrimidines
- Ro 28-2653
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- interleukin-22
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Topics |
- Animals
- Female
- Interleukin-17
(physiology)
- Interleukin-23
(physiology)
- Interleukins
(physiology)
- Intestine, Small
(immunology, pathology)
- Matrix Metalloproteinase 2
(physiology)
- Matrix Metalloproteinase 9
(physiology)
- Mice
- Mice, Inbred C57BL
- Piperazines
(pharmacology)
- Pyrimidines
(pharmacology)
- Toxoplasma
(pathogenicity)
- Toxoplasmosis, Animal
(immunology)
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