Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.

Abstract

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 TRM cells, 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+ TRM cells. 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.

• Authors: Vladimir-Andrey Gimenez-Rivera, Frank Siebenhaar, Carolin Zimmermann, Hanna Siiskonen, Martin Metz, Marcus Maurer
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 197 Issue 11 Pg. 4240-4246 (12 01 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 27807191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Allergens
• Cytokines
• Oxazolone
• Proto-Oncogene Proteins c-kit

Topics

• Allergens (immunology, toxicity)
• Animals
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Chronic Disease
• Cytokines (genetics, immunology)
• Dermatitis, Contact (genetics, immunology, pathology)
• Disease Models, Animal
• Immunologic Memory
• Mast Cells (immunology, pathology)
• Mice
• Mice, Transgenic
• Oxazolone (adverse effects, pharmacology)
• Proto-Oncogene Proteins c-kit (genetics, immunology)
• Skin (immunology, pathology)