TY - JOUR
T1 - Differential regulation of epidermal Langerhans cell migration by interleukins (IL)-1α and IL-1β during irritant- and allergen-induced cutaneous immune responses
AU - Cumberbatch, Marie
AU - Dearman, Rebecca J.
AU - Groves, Richard W.
AU - Antonopoulos, Christos
AU - Kimber, Ian
PY - 2002
Y1 - 2002
N2 - Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-18 are all known to contribute to the regulation of epidermal Langerhans cells (LC) migration and the subsequent accumulation of dendritic cells (DC) in draining lymph nodes following skin sensitization. However, the cytokine signals that control these responses following skin irritation have yet to be defined. We demonstrate that IL-1α, a cytokine associated with skin injury and inflammation, is able to stimulate the activation and migration from the epidermis of LC and their subsequent accumulation in skin-draining lymph nodes. Stimulation of these responses by IL-1α required the local availability of TNF-α. Using specific neutralizing antibodies, LC migration induced following skin sensitization with oxazolone (Ox) was found to be dependent upon IL-1β and independent of a requirement for IL-1α. However, the converse was true following stimulation of responses with the nonsensitizing skin irritant sodium lauryl sulfate (SLS). Here, the loss of LC from the epidermis and the accumulation of DC in draining lymph nodes required IL-1α and not IL-1β. Despite utilizing different IL-1 isoforms for LC mobilization, the phenotypic characteristics of DC arriving in draining lymph nodes in response to Ox and SLS were similar with respect to the membrane determinants MHC class II, B7-1, B7-2, and intercellular adhesion molecule-1. These data suggest that contact sensitization and skin irritation employ subtly different cytokine networks in the regulation of LC migration, both involving TNF-α but demonstrating differential requirements for IL-1 cytokines. The proposal is that different forms of cutaneous trauma may achieve LC migration through distinct molecular mechanisms. © 2002 Elsevier Science (USA).
AB - Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-18 are all known to contribute to the regulation of epidermal Langerhans cells (LC) migration and the subsequent accumulation of dendritic cells (DC) in draining lymph nodes following skin sensitization. However, the cytokine signals that control these responses following skin irritation have yet to be defined. We demonstrate that IL-1α, a cytokine associated with skin injury and inflammation, is able to stimulate the activation and migration from the epidermis of LC and their subsequent accumulation in skin-draining lymph nodes. Stimulation of these responses by IL-1α required the local availability of TNF-α. Using specific neutralizing antibodies, LC migration induced following skin sensitization with oxazolone (Ox) was found to be dependent upon IL-1β and independent of a requirement for IL-1α. However, the converse was true following stimulation of responses with the nonsensitizing skin irritant sodium lauryl sulfate (SLS). Here, the loss of LC from the epidermis and the accumulation of DC in draining lymph nodes required IL-1α and not IL-1β. Despite utilizing different IL-1 isoforms for LC mobilization, the phenotypic characteristics of DC arriving in draining lymph nodes in response to Ox and SLS were similar with respect to the membrane determinants MHC class II, B7-1, B7-2, and intercellular adhesion molecule-1. These data suggest that contact sensitization and skin irritation employ subtly different cytokine networks in the regulation of LC migration, both involving TNF-α but demonstrating differential requirements for IL-1 cytokines. The proposal is that different forms of cutaneous trauma may achieve LC migration through distinct molecular mechanisms. © 2002 Elsevier Science (USA).
KW - Contact allergy
KW - Interleukin 1
KW - Irritants
KW - Langerhans cells
KW - Skin
U2 - 10.1006/taap.2002.9442
DO - 10.1006/taap.2002.9442
M3 - Article
C2 - 12140176
VL - 182
SP - 126
EP - 135
JO - Toxicology and applied pharmacology
JF - Toxicology and applied pharmacology
SN - 0041-008X
IS - 2
ER -