Cutting Edge: IL-23 Cross-Regulates IL-12 Production in T Cell-Dependent Experimental Colitis
| Autor: | Stefan Wirtz, George D. Yancopoulos, Clemens Neufert, Christoph Becker, Massimo Fantini, Andrew J. Murphy, Heike Dornhoff, Margaret Karow, Hans-Anton Lehr, Peter R. Galle, David M. Valenzuela, Markus F. Neurath, Alexei Nikolaev, Sabine Huebner |
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| Rok vydání: | 2006 |
| Předmět: |
T-Lymphocytes
Transgene T cell Immunology Down-Regulation Mice Transgenic Interleukin-23 Pathogenesis Mice Interleukin 23 Animals Immunology and Allergy Medicine Colitis Cells Cultured business.industry Interleukins Experimental autoimmune encephalomyelitis medicine.disease Interleukin-12 Survival Rate Disease Models Animal Protein Subunits medicine.anatomical_structure Knockout mouse Interleukin-23 Subunit p19 Interleukin 12 Disease Susceptibility business |
| Zdroj: | The Journal of Immunology. 177:2760-2764 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.177.5.2760 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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