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 Kit (Sash) and MCPT5-CreiDTR 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 (T) cells. The CD8 T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous T 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 T 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.

Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia

“…Mast cells accumulate in affected tissues of C57BL/6 mice following repeated Ox challenges [ 16 , 27 , 28 ]. We noted a concomitant ~4-fold increase in the abundance of tissue mast cells at day 1 and a ~2-fold increase in total histamine content that persisted through day 21 after 10 labiar Ox challenges.…”

Mast cells as sources of cytokines, chemokines, and growth factors

“…However, inspection of the figures in the 2 papers indicated that, in addition to using different strains of MC‐deficient mice, the 2 groups were studying CHS responses of different severity and duration. This is important, in that Gimenez‐Rivera et al recently reported additional evidence, derived from studies using a different model of CHS tested in both “ Kit ‐dependent” and “ Kit ‐independent” MC‐deficient mice, that MCs can limit the features of this model CHS. Indeed, many different CHS models have been examined with various types of MC‐deficient mice, and the results obtained could be interpreted to indicate that, depending on the circumstances, MCs can enhance, suppress, or have no detectable effects on the features of the tested model …”

“…However, it now appears that MC IL-10 production also can contribute to immune regulation, at least in cer- COLOUR were studying CHS responses of different severity and duration. This is important, in that Gimenez-Rivera et al 163 In part to address the "controversy" regarding the different conclusions of the studies by Grimbaldeston et al 157 and Dudeck et al, 159 Reber et al 165…”

Imaging protective mast cells in living mice during severe contact hypersensitivity

“…By contrast, based on findings in both Kit-mutant and Kit-independent MC-deficient mice, Gimenez-Rivera et al recently reported that MCs can suppress skin inflammation in a new mouse model of chronic CHS (14).…”