Publications

Allergic contact dermatitis is a chronic T cell–driven inflammatory skin disease that is caused by repeated exposure to contactallergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its patho-genesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murinemodels for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type andMC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergiccontact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficientKitW-sh/W-sh(Sash) and MCPT5-Cre+iDTR+mice compared with wild-type mice. Local engraftment with MCs protected Sash mice fromexacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevatedlevels of IFN-g, IL-17a, and IL-23, as well as increased accumulation of Ag-specific IFN-g–producing CD8+tissue-residentmemory T (TRM) cells. The CD8+T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice duringthe accumulation of cutaneous TRMcells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skininflammation induced by repeated allergen challenge, at least in part, via effects on CD8+TRMcells. MCs may notably influencethe course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms maylead to better approaches for the treatment of this common, disabling, and costly condition.The Journal of Immunology,2016, 197: 4240–4246.