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

被引：231

作者：

Munoz, Melba ^{[1
]}

Heimesaat, Markus M. ^{[1
]}

Danker, Kerstin ^{[3
]}

Struck, Daniela ^{[1
]}

Lohmann, Uwe ^{[1
]}

Plickert, Rita ^{[1
]}

Bereswill, Stefan ^{[1
]}

Fischer, Andre ^{[1
]}

Dunay, Ildiko Rita ^{[1
,13
]}

Wolk, Kerstin ^{[4
]}

Loddenkemper, Christoph ^{[2
]}

Krell, Hans-Willi ^{[5
]}

Libert, Claude ^{[6
]}

Lund, Leif R. ^{[7
]}

Frey, Oliver ^{[8
]}

Hoelscher, Christoph ^{[9
]}

Iwakura, Yoichiro ^{[10
]}

Ghilardi, Nico ^{[11
]}

Ouyang, Wenjun ^{[12
]}

Kamradt, Thomas ^{[8
]}

Sabat, Robert ^{[4
]}

Liesenfeld, Oliver ^{[1
]}

机构：

[1] Charite, Inst Microbiol & Hyg, D-12203 Berlin, Germany

[2] Charite, Res Ctr ImmunoSci, Dept Pathol, D-12203 Berlin, Germany

[3] Charite, Inst Biochem, D-10117 Berlin, Germany

[4] Charite, Interdisciplinary Grp Mol Immunopathol, D-10117 Berlin, Germany

[5] Roche Diagnost GmbH, D-82377 Penzberg, Germany

[6] Univ Ghent VIB, Dept Mol Biomed Res, B-9052 Ghent, Belgium

[7] Univ Copenhagen, Fac Hlth Sci, Dept Cellular Mol Med, DK-2200 Copenhagen, Denmark

[8] Univ Jena, Sch Med, Inst Immunol, D-07743 Jena, Germany

[9] Res Ctr Borstel, D-23845 Borstel, Germany

[10] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan

[11] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA

[12] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA

[13] Univ Freiburg, Dept Neuropathol, D-79106 Freiburg, Germany

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2009年 / 206卷 / 13期

关键词：

INFLAMMATORY-BOWEL-DISEASE; T-CELL; MATRIX METALLOPROTEINASES; ORAL INFECTION; MURINE MODEL; TH17; CELLS; CUTTING EDGE; MOUSE MODEL; EXPRESSION; CYTOKINE;

D O I：

10.1084/jem.20090900

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：3047 / 3059

页数：13

共 57 条

[1] Enhanced inhibitory effect of the matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine and etoposide on the prostate carcinoma in the rat Dunning orthotopic tumor model [J].

Abramjuk, Claudia ;

Lein, Michael ;

Rothaug, Winfried ;

Krell, Hans-Willi ;

Loening, Stefan A. ;

Jung, Klaus .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2007, 59 (02) :275-282

[2] Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].

Aggarwal, S ;

Ghilardi, N ;

Xie, MH ;

de Sauvage, FJ ;

Gurney, AL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914

[3] Interleukin-17 in pulmonary host defense [J].

Aujla, Shean J. ;

Dubin, Patricia J. ;

Kolls, Jay K. .

EXPERIMENTAL LUNG RESEARCH, 2007, 33 (10) :507-518

[4] Expression of matrix metalloproteases in inflammatory bowel disease [J].

Baugh, MD ;

Evans, GS ;

Hollander, AP ;

Davies, DR ;

Perry, MJ ;

Lobo, AJ ;

Taylor, CJ .

INTESTINAL PLASTICITY IN HEALTH AND DISEASE, 1998, 859 :249-253

[5] Design, synthesis, and characterization of potent, slow-binding inhibitors that are selective for gelatinases [J].

Bernardo, MM ;

Brown, S ;

Li, ZH ;

Fridman, R ;

Mobashery, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :11201-11207

[6] TH-17 cells in the circle of immunity and autoimmunity [J].

Bettelli, Estelle ;

Oukka, Mohamed ;

Kuchroo, Vijay K. .

NATURE IMMUNOLOGY, 2007, 8 (04) :345-350

[7] Targeted deletion of metalloproteinase 9 attenuates experimental colitis in mice: Central role of epithelial-derived MMP [J].

Castaneda, FE ;

Walia, B ;

Vijay-Kumar, M ;

Patel, NR ;

Roser, S ;

Kolachala, VL ;

Rojas, M ;

Wang, LX ;

Oprea, G ;

Garg, P ;

Gewirtz, AT ;

Roman, J ;

Merlin, D ;

Sitaraman, SV .

GASTROENTEROLOGY, 2005, 129 (06) :1991-2008

[8] A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity [J].

Cella, Marina ;

Fuchs, Anja ;

Vermi, William ;

Facchetti, Fabio ;

Otero, Karel ;

Lennerz, Jochen K. M. ;

Doherty, Jason M. ;

Mills, Jason C. ;

Colonna, Marco .

NATURE, 2009, 457 (7230) :722-725

[9] Cutting edge:: IFN-γ regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection [J].

Cruz, Andrea ;

Khader, Shabaana A. ;

Torrado, Egidio ;

Fraga, Alexandra ;

Pearl, John E. ;

Pedrosa, Jorge ;

Cooper, Andrea M. ;

Castro, Antonio G. .

JOURNAL OF IMMUNOLOGY, 2006, 177 (03) :1416-1420

[10] Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain [J].

Cua, DJ ;

Sherlock, J ;

Chen, Y ;

Murphy, CA ;

Joyce, B ;

Seymour, B ;

Lucian, L ;

To, W ;

Kwan, S ;

Churakova, T ;

Zurawski, S ;

Wiekowski, M ;

Lira, SA ;

Gorman, D ;

Kastelein, RA ;

Sedgwick, JD .

NATURE, 2003, 421 (6924) :744-748

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