Soleto Irene, Ramirez Cristina, Gómez Cristina, Baldan-Martin Montse, Orejudo Macarena, Mercado Jorge, Chaparro María, Gisbert Javier P
Gastroenterology Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain.
Biomedicines. 2023 Oct 18;11(10):2831. doi: 10.3390/biomedicines11102831.
Inflammatory bowel disease (IBD) is a chronic condition which includes ulcerative colitis (UC) and Crohn's disease (CD), the origins of which are not yet fully understood. Both conditions involve an exacerbated immune response in the intestinal tract, leading to tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells crucial for maintaining tolerance in the gastrointestinal mucosa. Previous research has indicated that DC recruitment to the intestinal mucosa is more pronounced in individuals with IBD, but the specific mechanisms governing this migration remain unclear. This study aimed to assess the expression of various homing markers and the migratory abilities of circulating DC subsets in response to intestinal chemotactic signals. Additionally, this study examined how golimumab and ustekinumab impact these characteristics in individuals with IBD compared to healthy controls. The findings revealed that a particular subset of DCs known as type 2 conventional DCs (cDC2) displayed a more pronounced migratory profile compared to other DC subsets. Furthermore, the study observed that golimumab and ustekinumab had varying effects on the migratory profile of cDC1 in individuals with CD and UC. While CCL2 did not exert a chemoattractant effect on DC subsets in this patient cohort, treatment with golimumab and ustekinumab enhanced their migratory capacity towards CCL2 and CCL25 while reducing their migration towards MadCam1. In conclusion, this study highlights that cDC2 exhibits a heightened migratory profile towards the gastrointestinal mucosa compared to other DC subsets. This finding could be explored further for the development of new diagnostic biomarkers or the identification of potential immunomodulatory targets in the context of IBD.
炎症性肠病(IBD)是一种慢性疾病,包括溃疡性结肠炎(UC)和克罗恩病(CD),其病因尚未完全明确。这两种疾病都涉及肠道中加剧的免疫反应,导致组织炎症。树突状细胞(DC)是抗原呈递细胞,对维持胃肠道黏膜的耐受性至关重要。先前的研究表明,IBD患者中DC向肠道黏膜的募集更为明显,但控制这种迁移的具体机制仍不清楚。本研究旨在评估各种归巢标志物的表达以及循环DC亚群对肠道趋化信号的迁移能力。此外,本研究还考察了与健康对照相比,戈利木单抗和优特克单抗对IBD患者这些特征的影响。研究结果显示,一种称为2型传统DC(cDC2)的特定DC亚群与其他DC亚群相比,表现出更明显的迁移特征。此外,该研究观察到,戈利木单抗和优特克单抗对CD和UC患者的cDC1迁移特征有不同影响。虽然CCL2在该患者队列中对DC亚群没有趋化作用,但使用戈利木单抗和优特克单抗治疗可增强它们对CCL2和CCL25的迁移能力,同时减少它们向黏膜地址素细胞黏附分子1(MadCam1)的迁移。总之,本研究强调,与其他DC亚群相比,cDC2对胃肠道黏膜表现出更高的迁移特征。这一发现可进一步探索,用于开发新的诊断生物标志物或在IBD背景下识别潜在的免疫调节靶点。