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.
authors.affiliation: Institute of Microbiology and Hygiene, Campus Benjamin Franklin, Charité Medical School, 12203 Berlin, Germany.
authors.forename: Melba
authors.initials: M
authors.lastname: Muñoz
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.forename: Kerstin
authors.initials: K
authors.lastname: Danker
authors.forename: Daniela
authors.initials: D
authors.lastname: Struck
authors.forename: Uwe
authors.initials: U
authors.lastname: Lohmann
authors.forename: Rita
authors.initials: R
authors.lastname: Plickert
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.forename: Ildikò Rita
authors.initials: IR
authors.lastname: Dunay
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Krell
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
authors.forename: Leif R
authors.initials: LR
authors.lastname: Lund
authors.forename: Oliver
authors.initials: O
authors.lastname: Frey
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Nico
authors.initials: N
authors.lastname: Ghilardi
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Oliver
authors.initials: O
authors.lastname: Liesenfeld
mesh_terms: D000818:Animals; D005260:Female; D020381:Interleukin-17 / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology*; D007378:Interleukins / Q000502:physiology*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014122:Toxoplasma / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010879:Piperazines; D011743:Pyrimidines; D000097043:Interleukin-22; C453902:Ro 28-2653