BACKGROUND Epidermal hyperplasia represents a morphologic hallmark of psoriatic skin lesions. Langerhans cells (LCs) in the psoriatic epidermis engage with keratinocytes (KCs) in tight physical interactions; moreover, they induce T-cell-mediated immune responses critical to psoriasis. OBJECTIVE This study sought to improve the understanding of epidermal factors in psoriasis pathogenesis. METHODS BMP7-LCs versus TGF-β1-LCs were phenotypically characterized and their functional properties were analyzed using flow cytometry, cell kinetic studies, co-culture with CD4 T cells, and cytokine measurements. Furthermore, immunohistology of healthy and psoriatic skin was performed. Additionally, in vivo experiments with Junf/fJunBf/fK5cre-ERT mice were carried out to assess the role of bone morphogenetic protein (BMP) signaling in psoriatic skin inflammation. RESULTS This study identified a KC-derived signal (ie, BMP signaling) to promote epidermal changes in psoriasis. Whereas BMP7 is strictly confined to the basal KC layer in the healthy skin, it is expressed at high levels throughout the lesional psoriatic epidermis. BMP7 instructs precursor cells to differentiate into LCs that phenotypically resemble psoriatic LCs. These BMP7-LCs exhibit proliferative activity and increased sensitivity to bacterial stimulation. Moreover, aberrant high BMP signaling in the lesional epidermis is mediated by a KC intrinsic mechanism, as suggested from murine data and clinical outcome after topical antipsoriatic treatment in human patients. CONCLUSIONS These data indicate that available TGF-β family members within the lesional psoriatic epidermis preferentially signal through the canonical BMP signaling cascade to instruct inflammatory-type LCs and to promote psoriatic epidermal changes. Targeting BMP signaling might allow to therapeutically interfere with cutaneous psoriatic manifestations.

中文翻译：

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在银屑病表皮中异常诱导的BMP7指示与炎症相关的Langerhans细胞。

背景技术表皮增生代表银屑病皮肤病变的形态学标志。银屑病表皮中的朗格汉斯细胞（LC）与角质形成细胞（KC）紧密地相互作用。此外，它们诱导对牛皮癣至关重要的T细胞介导的免疫反应。目的本研究旨在增进对银屑病发病机制中表皮因子的认识。方法对BMP7-LCs与TGF-β1-LCs进行表型鉴定，并使用流式细胞术，细胞动力学研究，与CD4 T细胞共培养以及细胞因子测量分析其功能特性。此外，进行了健康和牛皮癣皮肤的免疫组织学。此外，对Junf / fJunBf / fK5cre-ERT小鼠进行了体内实验，以评估骨形态发生蛋白（BMP）信号传导在牛皮癣皮肤炎症中的作用。结果这项研究确定了KC衍生的信号（即BMP信号）来促进牛皮癣的表皮变化。尽管BMP7严格限制在健康皮肤的基底KC层中，但在整个损伤性牛皮癣表皮中都以高水平表达。BMP7指示前体细胞分化为表型类似于银屑病LC的LC。这些BMP7-LC表现出增殖活性，并增加了对细菌刺激的敏感性。此外，如通过人类患者局部银屑病治疗后的鼠类数据和临床结果所暗示的，病变表皮中异常高的BMP信号传导是由KC内在机制介导的。结论这些数据表明，病变性牛皮癣表皮中的可用TGF-β家族成员优先通过规范性BMP信号级联发出信号，以指导炎症型LC并促进牛皮癣表皮的改变。靶向BMP信号传导可能会在治疗上干扰皮肤银屑病表现。