Li Yi-Yang Yvonne, Zollner Thomas M, Schön Michael P
CRBA Inflammation/Immunology, Berlex Biosciences, Richmond, CA 94804, USA.
Clin Dermatol. 2008 Sep-Oct;26(5):527-38. doi: 10.1016/j.clindermatol.2007.11.002.
Tissue-selective recruitment of immunocytes to cutaneous tissues, a complex multistep cascade mediated by a large variety of cytokines, chemokines, and adhesion molecules, is thought to be a pivotal process in the pathogenesis of psoriasis. Following this notion, specifically targeting leukocyte trafficking remains an attractive approach for the treatment of psoriasis. It is increasingly recognized that during the pathogenesis of psoriasis not only effector T cells play important roles, but also multiple interactions between T cells, dendritic cells, macrophages, mast cells, endothelial cells, and keratinocytes are crucial for the full-fledged development of psoriasis. Meanwhile, the first biologics specifically inhibiting key molecules involved in cutaneous leukocyte recruitment have been approved for the treatment of psoriasis. It is, however, challenging to predict that molecules in this complex process with many redundant and/or functionally overlapping players will suffice as therapeutic targets. In this review, we will discuss the molecules and mechanisms involved in trafficking of different types of leukocytes and elucidate modes of action as well as therapeutic strategies of existing drugs and drug candidates.
免疫细胞向皮肤组织的组织选择性募集是一个由多种细胞因子、趋化因子和黏附分子介导的复杂多步骤级联反应，被认为是银屑病发病机制中的关键过程。基于这一观点，特异性靶向白细胞迁移仍然是治疗银屑病的一种有吸引力的方法。人们越来越认识到，在银屑病发病过程中，不仅效应T细胞发挥重要作用，而且T细胞、树突状细胞、巨噬细胞、肥大细胞、内皮细胞和角质形成细胞之间的多种相互作用对于银屑病的全面发展至关重要。同时，首批特异性抑制参与皮肤白细胞募集的关键分子的生物制剂已被批准用于治疗银屑病。然而，要预测在这个有许多冗余和/或功能重叠参与者的复杂过程中的分子是否足以作为治疗靶点具有挑战性。在这篇综述中，我们将讨论参与不同类型白细胞迁移的分子和机制，并阐明现有药物和候选药物的作用方式以及治疗策略。
