Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.
Allergic contact dermatitis is a chronic T cell-driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient KitW-sh/W-sh(Sash) and MCPT5-Cre+iDTR+mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-γ, IL-17α, and IL-23, as well as increased accumulation of Ag-specific IFN-γ-producing CD8+tissue-resident memory T (TRM) cells. The CD8+T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous TRMcells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8+TRMcells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition.
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, D-10405 Berlin, Germany.
Vladimir-Andrey
VA
Gimenez-Rivera
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, D-10405 Berlin, Germany.
Frank
F
Siebenhaar
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, D-10405 Berlin, Germany.
Carolin
C
Zimmermann
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, D-10405 Berlin, Germany.
Hanna
H
Siiskonen
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, D-10405 Berlin, Germany.
Martin
0000-0002-4070-9976
M
Metz
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, D-10405 Berlin, Germany marcus.maurer@charite.de.
Marcus
M
Maurer
D000485:Allergens / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007156:Immunologic Memory; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010081:Oxazolone / Q000009:adverse effects / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D016207:Cytokines; D010081:Oxazolone; D019009:Proto-Oncogene Proteins c-kit