title: IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis.
abstract: Langerhans cells (LC) migrate rapidly from epidermis to lymph node following epicutaneous application of antigen. In this study, we have explored the role of IL-18, a cytokine with structural similarities to IL-1 beta, in murine LC migration and contact hypersensitivity (CHS), which to oxazolone (OX) and 2-4,dinitrofluorobenzene (DNFB) was suppressed significantly in IL-18 knockout (IL-18-/-) mice and could be rescued by local intradermal administration of IL-18 prior to sensitization, suggesting that the defect in these mice was in the afferent phase of CHS. To determine the effect of IL-18 on LC migration, mice were treated topically with OX or DNFB, and remaining LC numbers were assessed. A significant decline in remaining epidermal LC occurred in wild-type (WT) mice but did not occur in IL-18-/- mice. Sodium lauryl sulfate, a nonantigenic LC migratory stimulus, induced equivalent LC migration in IL-18-/- and WT mice. In IL-18-/- mice, IL-1 beta and TNF-alpha were equally able to mobilize LC from epidermis, indicating that migration in response to these cytokines is not dependent on IL-18 and suggesting that IL-18 acts upstream of these cytokines in the initiation of antigen-induced LC migration. Moreover, IL-1 beta but not IL-18 was able to rescue the defective CHS response observed in caspase-1-/- mice, which have no functional IL-1 beta or IL-18. These data indicate that IL-18 is a key proximal mediator of LC migration and CHS, acting upstream of IL-1 beta and TNF-alpha, and may play a central role in regulation of cutaneous immune responses.
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, United Kingdom.
authors.forename: Christos
authors.initials: C
authors.lastname: Antonopoulos
authors.forename: Marie
authors.initials: M
authors.lastname: Cumberbatch
authors.forename: John B
authors.initials: JB
authors.lastname: Mee
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Wei
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Richard W
authors.initials: RW
authors.lastname: Groves
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000503:physiopathology*; D004139:Dinitrofluorobenzene / Q000633:toxicity; D004817:Epidermis / Q000276:immunology / Q000473:pathology*; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology; D007801:Langerhans Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010081:Oxazolone / Q000633:toxicity; D011994:Recombinant Proteins / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D020382:Interleukin-18; D053583:Interleukin-1beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D012967:Sodium Dodecyl Sulfate; D004139:Dinitrofluorobenzene; D020170:Caspase 1