Cho Kyung-Ah, Park Minhwa, Kim Yu-Hee, Woo So-Youn
Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea.
Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea.
Biochem Biophys Res Commun. 2017 Jun 10;487(4):856-861. doi: 10.1016/j.bbrc.2017.04.141. Epub 2017 Apr 27.
Although mast cells are traditionally thought to function as effector cells in allergic responses, they have increasingly been recognized as important regulators of various immune responses. Mast cells mature locally; thus, tissue-specific influences are important for promoting mast cell accumulation and survival in the skin and the gastrointestinal tract. In this study, we determined the effects of keratinocytes on mast cell accumulation during Th17-mediated skin inflammation. We observed increases in dermal mast cells in imiquimod-induced psoriatic dermatitis in mice accompanied by the expression of epidermal stem cell factor (SCF), a critical mast cell growth factor. Similar to mouse epidermal keratinocytes, SCF was highly expressed in the human HaCaT keratinocyte cell line following stimulation with IL-17. Further, keratinocytes promoted mast cell proliferation following stimulation with IL-17 in vitro. However, the effects of keratinocytes on mast cells were significantly diminished in the presence of anti-CD117 (stem cell factor receptor) blocking antibodies. Taken together, our results revealed that the Th17-mediated inflammatory environment promotes mast cell accumulation through keratinocyte-derived SCF.
尽管传统上认为肥大细胞在过敏反应中作为效应细胞发挥作用，但它们越来越被认为是各种免疫反应的重要调节因子。肥大细胞在局部成熟；因此，组织特异性影响对于促进肥大细胞在皮肤和胃肠道中的积累和存活很重要。在本研究中，我们确定了角质形成细胞在Th17介导的皮肤炎症过程中对肥大细胞积累的影响。我们观察到咪喹莫特诱导的小鼠银屑病性皮炎中真皮肥大细胞增加，同时伴有表皮干细胞因子（SCF）的表达，SCF是一种关键的肥大细胞生长因子。与小鼠表皮角质形成细胞相似，在用IL-17刺激后，人HaCaT角质形成细胞系中SCF高度表达。此外，角质形成细胞在体外经IL-17刺激后促进肥大细胞增殖。然而，在存在抗CD117（干细胞因子受体）阻断抗体的情况下，角质形成细胞对肥大细胞的作用显著减弱。综上所述，我们的结果表明，Th17介导的炎症环境通过角质形成细胞衍生的SCF促进肥大细胞积累。
