溃疡性结肠炎
结肠炎
淋巴系统
免疫学
损耗
医学
病理
生物
疾病
牙科
作者
Pablo Canales-Herrerías,Mathieu Uzzan,Akihiro Seki,Rafael S. Czepielewski,Bram Verstockt,Alexandra E. Livanos,Fiona Raso,Alexandra Dunn,Daniel S. Dai,Andrew Wang,Zainab Al-Taie,Jérôme C. Martin,Thomas Laurent,Huaibin M. Ko,Minami Tokuyama,Michael Tankelevich,Hadar Meringer,Francesca Cossarini,Divya Jha,Azra Krek
出处
期刊:Science immunology
[American Association for the Advancement of Science]
日期:2024-04-19
卷期号:9 (94)
被引量:13
标识
DOI:10.1126/sciimmunol.adg7549
摘要
Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7 + ) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of β7 + IgG + plasmablasts in circulation, as well as IgG + plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC.
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