关键词: Langerhans cells cell adhesion cell motility inflammation integrins live cell imaging

Mesh : Humans Fibronectins / metabolism Immunity Integrin alpha5 / metabolism Integrins / metabolism Langerhans Cells Lipopolysaccharides / pharmacology Monocytes

来  源:   DOI:10.1111/exd.15021

Abstract:
Langerhans cells (LCs) are mainly present in the epidermis and mucosa, and have important roles during skin infection. Migration of LCs to lymph nodes is essential for antigen presentation. However, due to the difficulties in isolating and culturing human LCs, it is not fully understood how LCs move and interact with the extracellular matrix (ECM) through their adhesion molecules such as integrin, during the immune responses. In this study, we aimed to investigate LC motility, cell shape and the role of integrin under inflammatory conditions using monocyte-derived Langerhans cells (moLCs) as a model. As a result, lipopolysaccharide (LPS) stimulation increased adhesion on fibronectin coated substrate and integrin α5 expression in moLCs. Time-lapse imaging of moLCs revealed that stimulation with LPS elongated cell shape, whilst decreasing their motility. Additionally, this decrease in motility was not observed when pre-treated with a neutralising antibody targeting integrin α5. Together, our data suggested that activation of LCs decreases their motility by promoting integrin α5 expression to enhance their affinity to the fibronectin, which may contribute to their migration during inflammation.
摘要:
朗格汉斯细胞(LCs)主要存在于表皮和粘膜,并在皮肤感染过程中发挥重要作用。LCs向淋巴结的迁移对于抗原呈递至关重要。然而,由于分离和培养人类LCs的困难,目前尚不完全了解LCs如何通过其粘附分子(如整合素)与细胞外基质(ECM)移动和相互作用,在免疫反应期间。在这项研究中,我们的目的是研究LC运动,使用单核细胞衍生的朗格汉斯细胞(moLCs)作为模型,在炎症条件下的细胞形状和整合素的作用。因此,脂多糖(LPS)刺激增加了moLC中纤连蛋白包被底物和整合素α5表达的粘附。moLCs的延时成像显示,用LPS刺激延长细胞形状,同时降低他们的运动性。此外,用靶向整合素α5的中和抗体预处理时未观察到运动性降低。一起,我们的数据表明,LCs的激活通过促进整合素α5的表达来增强其对纤连蛋白的亲和力来降低其运动性,这可能有助于它们在炎症期间的迁移。
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