Nickoloff B J, Griffiths C E, Barker J N
Department of Pathology, University of Michigan Medical Center, Ann Arbor 48109-0602.
J Invest Dermatol. 1990 Jun;94(6 Suppl):151S-157S. doi: 10.1111/1523-1747.ep12876134.
In 1986 it was discovered that cultured human keratinocytes, when treated with gamma interferon, attract and bind T lymphocytes and monocytes. More is now known about trafficking of inflammatory cells in the skin, with specific molecular details involving various cytokines, chemotactic factors, and adhesion molecules. One key element is the in vivo movement of T cells that express LFA-1 into the epidermis, and their subsequent binding to keratinocytes via the surface expression of intercellular adhesion molecule-1 (ICAM-1). This interaction represents a common immunologic pathway, which has been identified in a wide variety of different skin diseases. This review provides a synopsis of advances in this field, which have grown rapidly during the past few years, and adds recent results dealing with coordinate regulation at the gene-transcriptional level of keratinocyte chemotactic factor production and adhesion molecule expression. Moreover, epidermal keratinocytes appear to play a pre-eminent role in the skin, serving as transducing elements converting exogenously applied low-molecular-weight chemical stimuli such as phorbol ester and urushiol (the active ingredient in poison ivy extracts) into the production of endogenously derived immunoregulatory proteins. These keratinocyte-derived molecules may then influence immunocytes and endothelial cells to further amplify the inflammatory response. The identification of keratinocyte-derived molecules such as IL-8 and ICAM-1, which influence the chemotaxis and adherence of T cells, adds substantial evidence supporting an active participatory role for keratinocytes in cutaneous immunohomeostasis. Finally, we highlight the importance of these immunoregulatory molecules in two malignant cutaneous disorders (cutaneous T-cell lymphoma and basal-cell carcinoma) and attempt to integrate these new findings into novel pathophysiologic models for two inflammatory dermatoses (rhus dermatitis and psoriasis).
1986年人们发现，培养的人角质形成细胞经γ干扰素处理后，能吸引并结合T淋巴细胞和单核细胞。如今，我们对皮肤中炎症细胞的迁移了解得更多了，涉及各种细胞因子、趋化因子和黏附分子的具体分子细节也已明确。一个关键因素是表达淋巴细胞功能相关抗原-1（LFA-1）的T细胞在体内向表皮的迁移，以及它们随后通过细胞间黏附分子-1（ICAM-1）的表面表达与角质形成细胞结合。这种相互作用代表了一种常见的免疫途径，在多种不同的皮肤疾病中都已得到确认。这篇综述概述了该领域在过去几年中迅速发展的进展，并补充了有关角质形成细胞趋化因子产生和黏附分子表达在基因转录水平上的协同调控的最新研究结果。此外，表皮角质形成细胞似乎在皮肤中起着至关重要的作用，作为转导元件，将外源性应用的低分子量化学刺激物，如佛波酯和漆酚（毒葛提取物中的活性成分）转化为内源性免疫调节蛋白的产生。这些角质形成细胞衍生的分子随后可能影响免疫细胞和内皮细胞，进一步放大炎症反应。对角质形成细胞衍生的分子如白细胞介素-8（IL-8）和ICAM-1的鉴定，这些分子影响T细胞的趋化性和黏附，为角质形成细胞在皮肤免疫稳态中发挥积极参与作用提供了大量证据。最后，我们强调了这些免疫调节分子在两种皮肤恶性疾病（皮肤T细胞淋巴瘤和基底细胞癌）中的重要性，并试图将这些新发现整合到两种炎症性皮肤病（漆树皮炎和银屑病）的新病理生理模型中。
