Zundler Sebastian, Neurath Markus F
Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.
Inflamm Bowel Dis. 2017 Apr;23(4):617-627. doi: 10.1097/MIB.0000000000001067.
Therapeutic compounds interfering with T cell trafficking are a new column of inflammatory bowel disease (IBD) treatment. Currently, the anti-α4β7 integrin antibody vedolizumab is successfully used in the clinic and further drugs are likely to follow. Despite these clinical advances, the precise mechanistic background of their action is only gradually elucidated and still a matter of intensive research. Only recently, advances made with the help of new in vivo models and human studies have contributed to shape our concept of T cell trafficking in IBD by deciphering some important and so far unanswered questions. At the same time, basic and clinical data have generated new issues to be addressed on the way toward a clear perception of trafficking mechanisms and toward elucidation of the action of compounds interfering with this process. In this review, we will give a comprehensive outline of all components of T cell trafficking in regard to IBD before discussing the current knowledge concerning targeted interference with integrins in this complex network. Moreover, we will summarize remaining ambiguity and give an outlook on potential future targets.
干扰T细胞迁移的治疗性化合物是炎症性肠病(IBD)治疗的一个新领域。目前,抗α4β7整合素抗体维多珠单抗已成功应用于临床,可能还会有更多药物问世。尽管有这些临床进展,但其作用的确切机制背景仍在逐步阐明,仍是深入研究的课题。直到最近,借助新的体内模型和人体研究取得的进展,通过解答一些重要且迄今未得到解答的问题,才有助于塑造我们对IBD中T细胞迁移的概念。与此同时,基础和临床数据也产生了一些新问题,有待在明确了解迁移机制以及阐明干扰这一过程的化合物作用的道路上加以解决。在本综述中,我们将在讨论关于在这个复杂网络中靶向干扰整合素的现有知识之前,全面概述IBD中T细胞迁移的所有组成部分。此外,我们将总结尚存的模糊之处,并展望潜在的未来靶点。