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Lymphocyte trafficking to inflamed skin -- molecular mechanisms and implications for therapeutic target molecules.

机译:淋巴细胞向发炎皮肤的运输-分子机制及其对治疗靶分子的影响。

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摘要

Tissue-selective recruitment of lymphocytes to peripheral organs, such as the skin, is crucial for spatial compartmentalisation within the immune system as well as immune surveillance under normal conditions. In addition, this process plays a key role for the pathogenesis of various diseases including common inflammatory disorders such as atopic dermatitis or psoriasis, but also malignancies such as cutaneous T cell lymphomas. Recruitment of lymphocytes to the skin is a highly complex process that involves adhesion to the endothelial lining, extravasation, migration through the connective tissue, and, finally, localisation of a subpopulation of lymphocytes to the epithelial compartment, the epidermis. An intertwined network of constitutively expressed and inducible cytokines, chemokines and other mediators provides guidance for lymphocyte migration, and a large number of adhesion receptors mediate sequential steps of cell-cell- and cell-substrate-interactions resulting in tissue-specific localisation of immune cells. Selectively targeting the functions of one or several key molecules involved in this complex cascade promises exciting new therapeutic options for treating inflammatory disorders, but at the same time, bears considerable imponderables which will be discussed in this article.
机译:淋巴细胞向皮肤等周围器官的组织选择性募集对于免疫系统内的空间区分开以及正常条件下的免疫监视至关重要。另外,该过程对于多种疾病的发病机理起关键作用,所述疾病包括常见的炎性疾病,例如特应性皮炎或牛皮癣,而且还恶性肿瘤,例如皮肤T细胞淋巴瘤。淋巴细胞向皮肤的募集是一个高度复杂的过程,涉及粘附到内皮衬里,外渗,通过结缔组织迁移,最后将淋巴细胞亚群定位到上皮区室(表皮)。组成性表达和诱导型细胞因子,趋化因子和其他介体的相互缠绕的网络为淋巴细胞迁移提供了指导,并且大量的粘附受体介导了细胞-细胞与细胞-底物相互作用的顺序步骤,从而导致免疫细胞的组织特异性定位。选择性靶向这一复杂级联反应中涉及的一个或几个关键分子的功能,有望为治疗炎症性疾病提供令人兴奋的新治疗选择,但与此同时,本文将讨论许多不可思议的问题。

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