IL-23 and TH17-mediated inflammation in human allergic contact dermatitis
IL-23 and TH17-mediated inflammation in human allergic contact dermatitis
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DOI：
10.1016/j.jaci.2008.09.036
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发表时间：
2009-02-01
影响因子：
14.2
通讯作者：
Skov, Lone
中科院分区：
文献类型：
--
作者：
Larsen, Jeppe Madura;Bonefeld, Charlotte Menne;Skov, Lone
背景：产生IL-17的T-H（T（H）17）细胞是小鼠慢性炎症的关键介质。近年来的研究表明，T（H）17介导的炎症反应参与了人类自身免疫性疾病的发病机制，但T（H）17细胞在变应性疾病中的作用仍不明确。特别是，角质形成细胞对接触性过敏原的先天反应，过敏原特异性T（H）17细胞的诱导，方法：用镍刺激体外培养的人角质形成细胞，用定量PCR和ELISA方法检测IL-23和IL-12的产生。通过使用短期离体测定鉴定和表征来自镍过敏个体和健康对照的血液的过敏原特异性记忆T细胞。镍斑试验皮损和正常皮肤的T（H）17相关细胞和分子的表达进行了分析，通过使用免疫组化。结果：角朊细胞被发现产生IL-23，但没有检测到IL-12，在响应镍刺激。从镍过敏个体的外周血中分离的记忆T细胞，而不是健康对照，含有T（H）17和T（H）1细胞增殖响应镍脉冲DC。结论：T（H）17介导的免疫病理过程参与了人类变应性接触性皮炎的发生，包括对接触性变应原的先天性和获得性免疫应答。（J Allergy Clin Immunol 2009;123：486-92.）
Background: IL-17-producing T-H (T(H)17) cells are key mediators of chronic inflammation in mice. Recent studies have implicated T(H)17-mediated inflammation in the pathogenesis of human autoimmune diseases; however, the involvement of T(H)17 cells in allergic disorders remains largely elusive.Objective: To investigate T(H)17-mediated inflammation in human beings with allergic contact dermatitis; in particular, the innate response of keratinocytes to contact allergen, the induction of allergen-specific T(H)17 cells, and the presence of T(H)17-related effector cells in inflamed skin.Methods: Human keratinocytes were stimulated with nickel in vitro followed by measurements of IL-23 and IL-12 production by quantitative PCR and ELISA. Allergen-specific memory T cells from the blood of individuals with nickel allergy and healthy controls were identified and characterized by using a short-term ex vivo assay. Nickel patch test lesions and normal skin were analyzed for the expression of T(H)17-related cells and molecules by using immunohistochemistry.Results: Keratinocytes were found to produce IL-23, but no detectable IL-12, in a response to nickel stimulation. Memory T cells isolated from peripheral blood of individuals with nickel allergy, but not healthy controls, contained T(H)17 and T(H)1 cells proliferating in response to nickel-pulsed DCs. Inflamed skin of nickel-challenged allergic individuals contained infiltrating neutrophils and cells expressing IL-17, IL-22, CCR6, and IL-22R.Conclusion: Our results demonstrate the involvement of T(H)17-mediated immunopathology in human allergic contact dermatitis, including both innate and adaptive immune responses to contact allergens. (J Allergy Clin Immunol 2009;123:486-92.)