Laboratory of Genome and Biosignals, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
Biochem Biophys Res Commun. 2019 Apr 2;511(2):330-335. doi: 10.1016/j.bbrc.2019.02.046. Epub 2019 Feb 18.
Irritant contact dermatitis (ICD) is one of the most common inflammatory skin diseases caused by exposure to chemical irritants. Since chemical irritants primarily damage keratinocytes, these cells play a pivotal role in ICD. One of the phosphoinositide-metabolizing enzymes, phospholipase C (PLC) δ1, is abundantly expressed in keratinocytes. However, the role of PLCδ1 in ICD remains to be clarified. Here, we found that croton oil (CrO)-induced ear swelling, a feature of ICD, was attenuated in keratinocyte-specific PLCδ1 knockout mice (PLCδ1 cKO mice). Dendritic epidermal T cells (DETCs), which have a protective role against ICD, were activated in the epidermis of the PLCδ1 cKO mice. In addition, the skin of CrO-treated PLCδ1 cKO mice showed increased infiltration of Gr1CD11b myeloid cells. Of note, elimination of Gr1CD11b myeloid cells restored CrO-induced ear swelling in PLCδ1 cKO mice to a similar level as that in control mice. Taken together, our results strongly suggest that epidermal loss of PLCδ1 protects mice from ICD through induction of Gr1CD11b myeloid cells and activation of DETCs.
刺激性接触性皮炎（ICD）是一种由化学刺激物暴露引起的最常见的炎症性皮肤病之一。由于化学刺激物主要损伤角质形成细胞，因此这些细胞在 ICD 中起着关键作用。一种磷酸肌醇代谢酶，即 PLCδ1，在角质形成细胞中大量表达。然而，PLCδ1 在 ICD 中的作用仍有待阐明。在这里，我们发现，蓖麻油（CrO）诱导的耳肿胀是 ICD 的一个特征，在角质形成细胞特异性 PLCδ1 敲除小鼠（PLCδ1 cKO 小鼠）中得到了减轻。树突状表皮 T 细胞（DETCs）在表皮中具有对抗 ICD 的保护作用，在 PLCδ1 cKO 小鼠的表皮中被激活。此外，在 CrO 处理的 PLCδ1 cKO 小鼠的皮肤中，Gr1CD11b 髓样细胞的浸润增加。值得注意的是，消除 Gr1CD11b 髓样细胞可使 PLCδ1 cKO 小鼠的 CrO 诱导的耳肿胀恢复到与对照小鼠相似的水平。综上所述，我们的研究结果强烈表明，表皮中 PLCδ1 的缺失通过诱导 Gr1CD11b 髓样细胞和激活 DETCs 来保护小鼠免受 ICD 的影响。
