Background

As well as thymic stromal lymphopoietin (TSLP) and IL-33, IL-25 is known to induce Th2 cytokine production by various cell types—including Th2 cells, Th9 cells, invariant NKT cells and group 2 innate lymphoid cells—involved in Th2-type immune responses. Since both Th2-type and Th17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 may contribute to this by enhancing Th2-type immune responses. However, the precise role of IL-25 in the pathogenesis of FITC-induced CHS is poorly understood.

Objective

We investigated the contribution of IL-25 to CHS using Il25^-/- mice.

Methods

CHS was evaluated by measurement of ear skin thickness in mice after FITC-painting. Skin dendritic cell (DC) migration, hapten-specific Th cell differentiation and detection of IL-1β-producing cells were determined by flow cytometry, ELISA and immunohistochemistry, respectively.

Results

In contrast to TSLP, we found that IL-25 was not essential for skin DC migration or hapten-specific Th cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell- and non-immune cell-derived IL-25 was important for hapten-specific Th17 cell-, rather than Th2 cell-, mediated inflammation in the elicitation phase of CHS by enhancing Th17-related, but not Th2-related, cytokines in the skin. In particular, IL-1β produced by dermal DCs in response to IL-25 was crucial for hapten-specific Th17 cell activation, contributing to induction of local inflammation in the elicitation phase of CHS.

Conclusion

Our results identify a novel IL-25 inflammatory pathway involved in induction of Th17, but not Th2, cell-mediated CHS. IL-25 neutralization may be a potential approach for treatment of CHS.

中文翻译：

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IL-25通过促进真皮树突状细胞产生IL-1β来增强Th17细胞介导的接触性皮炎

背景

与胸腺基质淋巴细胞生成素（TSLP）和IL-33一样，已知IL-25可以通过Th2参与的各种细胞类型（包括Th2细胞，Th9细胞，不变的NKT细胞和第2组先天淋巴样细胞）诱导Th2细胞因子的产生。类型的免疫反应。由于Th2型和Th17型细胞/细胞因子均对接触超敏反应（CHS）至关重要，因此IL-25可能会通过增强Th2型免疫反应而对此做出贡献。但是，人们对IL-25在FITC诱导的CHS发病机理中的确切作用了解甚少。

客观的

我们使用Il25 ^-/-小鼠调查了IL-25对CHS的贡献。

方法

通过测量FITC涂漆后小鼠的耳朵皮肤厚度来评估CHS。分别通过流式细胞术，ELISA和免疫组织化学测定皮肤树突状细胞（DC）的迁移，半抗原特异性Th细胞的分化以及产生IL-1β的细胞的检测。

结果

与TSLP相反，我们发现IL-25对CHS致敏期的皮肤DC迁移或半抗原特异性Th细胞分化不是必需的。出乎意料的是，肥大细胞和非免疫细胞来源的IL-25对于CHS诱导阶段中半抗原特异性Th17细胞而非Th2细胞介导的炎症很重要，因为它可以增强Th17相关而非Th2相关，皮肤中的细胞因子。特别地，由真皮DC响应IL-25而产生的IL-1β对于半抗原特异性的Th17细胞活化至关重要，有助于在CHS的诱导阶段诱导局部炎症。

结论

我们的结果确定了一种新的IL-25炎性途径，该途径与Th17诱导的细胞介导的CHS无关，但与Th2诱导的参与。IL-25中和可能是治疗CHS的潜在方法。