Chapter category: Immunology
Dendritic Cells As a Target for Therapeutic Intervention of Contact Hypersensitivity
Immune Mechanisms of Allergic Contact Dermatitis
Edited by: Andrea CavaniISBN: 1-58706-209-7
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Chapter authors:
Akira Takashima, Hiroyuki Matsue, Tadashi Kumamoto, Norikatsu Mizumoto, Akimichi Morita and Mark E. Mummert
Langerhans cells (LC), a skin-specific member of the dendritic cell (DC) family of antigen presenting cells, play crucial roles in the induction of allergic contact hypersensitivity responses (CHSR). Skin exposure to reactive haptens causes LC emigration from the epidermis as well as their maturation. Once the hapten-loaded, mature LC reach to draining lymph node, they deliver activation signals to hapten-reactive T cells, thereby triggering their clonal expansion. Our working hypothesis is, therefore, that LC serve as a potential target for therapeutic intervention of allergic contact dermatitis. Indeed, we have recently developed three strategies that are designed to prevent the onset of allergic CHSR by altering different aspects of LC function. First, we have isolated a 12-mer peptide, termed ÒPep-1Ó, which selectively binds to and inhibits the function of hyaluronan. Local administration of Pep-1 in mice prevented hapten-triggered LC migration from the epidermis, thereby inhibiting CHSR at the elicitation phase. Secondly, we have converted DC into tolerogenic DC by introducing cDNA encoding CD95L. Upon in vivo administration, the resulting ÒkillerÓ DC suppressed CHSR in a hapten-specific manner by eliminating hapten-reactive T cells. Finally, we have observed that LC in CD39-deficient mice expressed no detectable ecto-ATPase/ADPase activities and that these mice exhibited severely impaired CHSR. Thus, CD39, which is responsible for LC-associated ecto-ATPase/ADPase activities, may serve as a therapeutic target for allergic contact dermatitis. Taken together, our findings support the concept that allergic CHSR can be manipulated experimentally by altering the function of LC.
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