title: Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis.
abstract: Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. Finally, in vivo blockade of IL-12 p40 in IL-23-deficient mice rescued mice from lethal colitis. Taken together, our data identify cross-regulation of IL-12 expression by IL-23 as novel key regulatory pathway during initiation of T cell dependent colitis.
authors.affiliation: Laboratory of Immunology, First Medical Clinic, University of Mainz, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker
authors.forename: Heike
authors.initials: H
authors.lastname: Dornhoff
authors.forename: Clemens
authors.initials: C
authors.lastname: Neufert
authors.forename: Massimo C
authors.initials: MC
authors.lastname: Fantini
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirtz
authors.forename: Sabine
authors.initials: S
authors.lastname: Huebner
authors.forename: Alexei
authors.initials: A
authors.lastname: Nikolaev
authors.forename: Hans-Anton
authors.initials: HA
authors.lastname: Lehr
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Margaret
authors.initials: M
authors.lastname: Karow
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015536:Down-Regulation; D018664:Interleukin-12 / Q000096:biosynthesis*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D021122:Protein Subunits; D018664:Interleukin-12