Fas Ligand Induces Cell-Autonomous IL-23 Production in Dendritic Cells, a Mechanism for Fas Ligand-Induced IL-17 Production
| Autor: | Takashi Suda, Ryu Imamura, Hiroyasu Kidoya, Ayano Yahagi, Goro Matsuzaki, Takaya Kawabe, Masayuki Umemura |
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| Rok vydání: | 2005 |
| Předmět: |
Fas Ligand Protein
Immunology chemical and pharmacologic phenomena Inflammation Interleukin-23 Fas ligand Proinflammatory cytokine Mice In vivo Tumor Cells Cultured Interleukin 23 medicine Animals Humans Immunology and Allergy Membrane Glycoproteins Chemistry Interleukins Interleukin-17 hemic and immune systems Dendritic Cells Coculture Techniques In vitro Cell biology medicine.anatomical_structure Tumor Necrosis Factors Interleukin-23 Subunit p19 Bone marrow Interleukin 17 Peritoneum medicine.symptom Interleukin-1 |
| Zdroj: | The Journal of Immunology. 175:8024-8031 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.175.12.8024 |
| Popis: | Fas ligand (FasL) has the potential to induce inflammation accompanied by massive neutrophil infiltration. We previously reported that FasL rapidly induces the production of various inflammatory cytokines including IL-1β and IL-17. In this study, we investigated the mechanism of the FasL-induced IL-17 production. We found that the culture supernatant of mouse resident peritoneal exudate cells (PEC) cocultured with FasL-expressing tumor (FFL) cells induced IL-17 production in freshly isolated resident PEC. Anti-IL-1β Ab strongly inhibited the IL-17-inducing activity. However, rIL-1β by itself induced only weak IL-17 production. Intriguingly, anti-IL-12 Ab but not an IL-15-neutralizing agent, IL15R-Fc, strongly inhibited the FasL-induced IL-17-inducing activity. IL-23, which shares the p40 subunit with IL-12, but not IL-12 itself, induced IL-17 production synergistically with IL-1β in resident PEC. FasL induced the production of IL-23 in PEC in vivo and in vitro, and IL-17 production following the i.p. injection of FFL cells was severely impaired in p40−/− mice, indicating that IL-23 plays an important role in the FasL-induced IL-17 production. FFL also induced the production of IL-23 in bone marrow- or PEC-derived dendritic cells (DCs). Finally, FasL induced only weak p40 production in a mixture of p40−/− and Fas−/− DC, indicating that FasL induces IL-23 production in DC mainly in a cell-autonomous manner. |
| Databáze: | OpenAIRE |
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