Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Exp Dermatol. 2019 Aug;28(8):948-955. doi: 10.1111/exd.13984. Epub 2019 Jul 3.
Irritant contact dermatitis (ICD) is characterized by epidermal hyperplasia, infiltration of leucocytes into lesional skin and inflammatory cytokine release. The cellular infiltrate during ICD comprises primarily cells of the myeloid lineage. Our group has previously shown that the cytokine IL-6 confers a protective effect to lesional skin during ICD. How IL-6Rα function in myeloid cells is involved in the inflammatory response during ICD is, however, unknown. In the present study, utilizing a chemical model of ICD, it is shown that mice with a myeloid-specific knockout of the IL-6Rα (IL-6Rα ) display an exaggerated inflammatory response to benzalkonium chloride (BKC) and Jet propellant-8 (JP8) fuel, two well-characterized irritants relative to littermate control. Results from immunohistochemical and flow cytometric analyses revealed that IL-6Rα mouse skin displayed increased epidermal hyperplasia and inflammatory monocyte influx into lesional skin but lower numbers of resident macrophages relative to littermate controls after irritant exposure. Multiplex immunoassay revealed significantly higher levels of pro-inflammatory cytokines IL-1α and TNF-α, but reduced expression of chemokine proteins including CCL2-5, CCL7, CCL11, CXCL1 and CXCL10 in IL-6Rα mouse skin relative to littermate control following irritant exposure. These results highlight a previously unknown role of IL-6Rα function in myeloid cells in modulating the inflammatory response and myeloid population dynamics during ICD.
刺激性接触性皮炎（ICD）的特征是表皮增生、白细胞浸润到皮损皮肤和炎症细胞因子释放。ICD 期间的细胞浸润主要由髓系细胞组成。我们的研究小组之前已经表明，细胞因子 IL-6 在 ICD 期间对皮损皮肤具有保护作用。然而，IL-6Rα 在髓系细胞中的功能如何参与 ICD 期间的炎症反应尚不清楚。在本研究中，利用 ICD 的化学模型，我们表明，与同窝对照相比，髓系特异性敲除 IL-6Rα（IL-6Rα）的小鼠对苯扎氯铵（BKC）和喷气推进剂-8（JP8）燃料（两种公认的刺激性物质）表现出过度的炎症反应。免疫组织化学和流式细胞术分析的结果表明，与同窝对照相比，IL-6Rα 小鼠皮肤在受到刺激后表现出更高的表皮增生和炎症性单核细胞浸润到皮损皮肤，但驻留巨噬细胞的数量较低。多重免疫分析显示，与同窝对照相比，IL-6Rα 小鼠皮肤在受到刺激后，促炎细胞因子 IL-1α 和 TNF-α 的水平显著升高，但趋化因子蛋白包括 CCL2-5、CCL7、CCL11、CXCL1 和 CXCL10 的表达降低。这些结果强调了 IL-6Rα 在髓系细胞中的功能在调节 ICD 期间炎症反应和髓系细胞群体动力学方面的先前未知作用。
