Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17

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

doi:10.1084/jem.20090900

Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17

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 KamradtRobert Sabat, Oliver Liesenfeld

Glycomics Program

189 Citations (Scopus)

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.

Original language	English
Journal	Journal of Experimental Medicine
Volume	206
Issue number	13
Pages (from-to)	3047-59
Number of pages	12
ISSN	0022-1007
DOIs	https://doi.org/10.1084/jem.20090900
Publication status	Published - 2009

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Muñoz, M., Heimesaat, M. M., Danker, K., Struck, D., Lohmann, U., Plickert, R., Bereswill, S., Fischer, A., Dunay, I. R., Wolk, K., Loddenkemper, C., Krell, H-W., Libert, C., Lund, L. R., Frey, O., Hölscher, C., Iwakura, Y., Ghilardi, N., Ouyang, W., ... Liesenfeld, O. (2009). Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. Journal of Experimental Medicine, 206(13), 3047-59. https://doi.org/10.1084/jem.20090900

Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. / Muñoz, Melba; Heimesaat, Markus M; Danker, Kerstin et al.

In: Journal of Experimental Medicine, Vol. 206, No. 13, 2009, p. 3047-59.

Research output: Contribution to journal › Journal article › Research › peer-review

Muñoz, M, Heimesaat, MM, Danker, K, Struck, D, Lohmann, U, Plickert, R, Bereswill, S, Fischer, A, Dunay, IR, Wolk, K, Loddenkemper, C, Krell, H-W, Libert, C, Lund, LR, Frey, O, Hölscher, C, Iwakura, Y, Ghilardi, N, Ouyang, W, Kamradt, T, Sabat, R & Liesenfeld, O 2009, 'Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17', Journal of Experimental Medicine, vol. 206, no. 13, pp. 3047-59. https://doi.org/10.1084/jem.20090900

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title = "Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17",

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.",

author = "Melba Mu{\~n}oz and Heimesaat, {Markus M} and Kerstin Danker and Daniela Struck and Uwe Lohmann and Rita Plickert and Stefan Bereswill and Andr{\'e} Fischer and Dunay, {Ildik{\`o} Rita} and Kerstin Wolk and Christoph Loddenkemper and Hans-Willi Krell and Claude Libert and Lund, {Leif R} and Oliver Frey and Christoph H{\"o}lscher and Yoichiro Iwakura and Nico Ghilardi and Wenjun Ouyang and Thomas Kamradt and Robert Sabat and Oliver Liesenfeld",

note = "Keywords: Animals; Female; Interleukin-17; Interleukin-23; Interleukins; Intestine, Small; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Piperazines; Pyrimidines; Toxoplasma; Toxoplasmosis, Animal",

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AU - Muñoz, Melba

AU - Heimesaat, Markus M

AU - Danker, Kerstin

AU - Struck, Daniela

AU - Lohmann, Uwe

AU - Plickert, Rita

AU - Bereswill, Stefan

AU - Fischer, André

AU - Dunay, Ildikò Rita

AU - Wolk, Kerstin

AU - Loddenkemper, Christoph

AU - Krell, Hans-Willi

AU - Libert, Claude

AU - Lund, Leif R

AU - Frey, Oliver

AU - Hölscher, Christoph

AU - Iwakura, Yoichiro

AU - Ghilardi, Nico

AU - Ouyang, Wenjun

AU - Kamradt, Thomas

AU - Sabat, Robert

AU - Liesenfeld, Oliver

N1 - Keywords: Animals; Female; Interleukin-17; Interleukin-23; Interleukins; Intestine, Small; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Piperazines; Pyrimidines; Toxoplasma; Toxoplasmosis, Animal

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20090900

DO - 10.1084/jem.20090900

M3 - Journal article

C2 - 19995958

SN - 0022-1007

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SP - 3047

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JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

IS - 13

ER -

Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17

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