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RESEARCH PRODUCT
Cutting Edge: IL-23 Cross-Regulates IL-12 Production in T Cell-Dependent Experimental Colitis
Stefan WirtzGeorge D. YancopoulosClemens NeufertChristoph BeckerMassimo FantiniAndrew J. MurphyHeike DornhoffMargaret KarowHans-anton LehrPeter R. GalleDavid M. ValenzuelaMarkus F. NeurathAlexei NikolaevSabine Huebnersubject
T-LymphocytesTransgeneT cellImmunologyDown-RegulationMice TransgenicInterleukin-23PathogenesisMiceInterleukin 23AnimalsImmunology and AllergyMedicineColitisCells Culturedbusiness.industryInterleukinsExperimental autoimmune encephalomyelitisColitismedicine.diseaseInterleukin-12Survival RateDisease Models AnimalProtein Subunitsmedicine.anatomical_structureImmunologyKnockout mouseInterleukin-23 Subunit p19Interleukin 12Disease Susceptibilitybusinessdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-08-22 | The Journal of Immunology |