Contribution of Langerhans cell-derived IL-18 to contact hypersensitivity
| Autor: | Brandon G. Howell, Qinchao Cai, Claudio Feliciani, Binghe Wang, Hideaki Watanabe, Irwin Freed, Daniel N. Sauder |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Langerhans cell
medicine.medical_treatment Immunology Biology Administration Cutaneous Dermatitis Contact Cell Line Interferon-gamma Mice Cell Movement medicine Immunology and Allergy Animals Interferon gamma RNA Messenger Mice Knockout integumentary system Immune Sera Caspase 1 Interleukin-18 Oxazolone Dendritic cell Molecular biology Interleukin-12 In vitro Up-Regulation Mice Inbred C57BL medicine.anatomical_structure Cytokine Cell culture Langerhans Cells Interleukin 12 Interleukin 18 Immunization Lymph Nodes Haptens Injections Intraperitoneal medicine.drug |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 168(7) |
| ISSN: | 0022-1767 |
| Popis: | The epidermal Langerhans cells (LC), a member of the dendritic cell family, and the LC-derived cytokine IL-12 play a pivotal role in the initiation of contact hypersensitivity (CHS), a Th1 immune response in the skin. Because IL-18, another LC-derived cytokine, shares functional and biological properties with IL-12, we examined a potential role for IL-18 in CHS initiation. Our studies demonstrated that during the induction phase of murine CHS, IL-18 mRNA was significantly up-regulated in the skin-draining lymph nodes (LN). Migratory hapten-modified LC in LN expressed high levels of IL-18 mRNA and secreted functional IL-18 protein. LN cells produced significant amounts of IFN-γ following in vitro IL-12 stimulation, which could be partially blocked by anti-IL-18 Ab, suggesting a synergistic role for endogenous IL-18 in IFN-γ production by LN cells. Because mature IL-18 requires cleavage of immature precursors by caspase-1, we further examined IL-12-induced IFN-γ production in caspase-1−/− LN cells. An impaired IFN-γ production was seen in caspase-1−/− LN cells, which could be restored by addition of exogenous IL-18, supporting a role for caspase-1-cleaved, mature IL-18 in IFN-γ production. Finally, in vivo studies showed that CHS responses were significantly inhibited in mice treated with neutralizing IL-18 Ab as well as in caspase-1−/− mice deficient in mature IL-18, indicating functional relevance for IL-18 in CHS. Taken together, our studies demonstrate that LC-derived IL-18 significantly contributes to CHS initiation. |
| Databáze: | OpenAIRE |
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