TY - JOUR
T1 - IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis
AU - Antonopoulos, C
AU - Cumberbatch, M
AU - Mee, J B
AU - Dearman, R J
AU - Wei, X Q
AU - Liew, F Y
AU - Kimber, I
AU - Groves, R W
PY - 2008/2/2
Y1 - 2008/2/2
N2 - 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
AB - 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
U2 - 10.1189/jlb.0604352
DO - 10.1189/jlb.0604352
M3 - Article
VL - 83
SP - 361
EP - 367
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 2
ER -