Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure
Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure
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DOI：
10.4049/jimmunol.1600236
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发表时间：
2016-12-01
影响因子：
4.4
通讯作者：
Maurer, Marcus
中科院分区：
文献类型：
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作者：
Gimenez-Rivera, Vladimir-Andrey;Siebenhaar, Frank;Maurer, Marcus
过敏性接触性皮炎是一种慢性T细胞驱动的炎症性皮肤病，由反复暴露于接触性过敏原引起。基于小鼠急性接触性超敏反应的研究，认为肥大细胞（MC）在其发病机制中起作用。MC在慢性变应性接触性皮炎中的作用尚未研究，部分原因是缺乏慢性接触性超敏反应的小鼠模型。我们在野生型和MC缺陷小鼠中开发并使用了慢性接触性超敏反应模型，并评估了皮肤炎症反应，以确定和表征MC在慢性过敏性接触性皮炎中的作用。与野生型小鼠相比，MC缺陷型Kit（w-shiw-sh）（Sash）和MCPT 5-Cre（+）iDTR（+）小鼠的耳肿胀慢性接触性超敏反应显著增加，高达4倍。局部植入MC保护Sash小鼠在重复恶唑酮攻击后免于加重耳肿胀。Sash小鼠的慢性接触性超敏反应皮肤表现出IFN-γ、IL-17 α和IL-23水平升高，以及产生Ag特异性IFN-γ的CD 8（+）组织驻留记忆T（T-Rm）细胞的积累增加。CD 8（+）T细胞有丝分裂原IL-15在恶唑酮攻击的Sash小鼠皮肤中在皮肤TRm细胞积累期间增加，在体外被MCs有效降解。MCs至少部分通过对CD 8（+）TRm细胞的作用，防止由反复过敏原攻击诱导的加重的过敏性皮肤炎症。MCs可能显著影响慢性变应性接触性皮炎的病程。更好地了解它们的作用和潜在的机制可能会导致更好的方法来治疗这种常见的，致残的和昂贵的条件。
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(w-shiw-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-gamma, IL-17 alpha, and IL-23, as well as increased accumulation of Ag-specific IFN-gamma producing CD8(+) tissue-resident memory T (T-Rm) 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.