Moraes Holst Luiza, Halfvarson Jonas, Carlson Marie, Hedin Charlotte, Kruse Robert, Lindqvist Carl Mårten, Bergemalm Daniel, Almér Sven, Bresso Francesca, Ling Lundström Maria, Repsilber Dirk, D'Amato Mauro, Keita Åsa, Hjortswang Henrik, Söderholm Johan, Sundin Johanna, Törnblom Hans, Simrén Magnus, Strid Hans, Magnusson Maria K, Öhman Lena
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Clin Exp Gastroenterol. 2022 Jul 27;15:129-144. doi: 10.2147/CEG.S368040. eCollection 2022.
Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).
Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.
The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.
This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.
为了开发治疗和预防炎症性肠病（IBD）发作的治疗方案，需要改善活动性和静止期结肠IBD的黏膜免疫谱。因此，本研究旨在提供全面的黏膜特征描述，重点关注活动性溃疡性结肠炎（UC活动期）、UC缓解期和活动性结肠克罗恩病（CD活动期）患者的免疫宿主反应。
收集47名研究对象的结肠活检组织，使用NanoString宿主反应分析板进行基因表达和通路分析，该分析板包括776个基因和56条免疫相关通路。
与健康受试者（n = 10）相比，活动性IBD（n = 27）中大多数黏膜基因表达和信号通路得分增加。然而，与健康受试者相比，活动性IBD和UC缓解期（n = 10）均显示出自噬、α激酶-1和IL-17信号通路相关的基因表达和信号通路得分降低。此外，与健康受试者相比，UC缓解期的特征是与内环境稳定相关的几条信号通路得分降低，同时单核细胞迁移通路得分增加。未观察到CD活动期（n = 7）和UC活动期（n = 20）之间结肠黏膜基因表达的主要差异。
本研究表明，无论疾病活动状态如何，自噬、α激酶-1和IL-17信号通路在UC中持续下调。此外，缓解期的UC患者呈现出独特的黏膜环境，这可能使患者无法达到并维持真正的内环境稳定。这些发现可能有助于更好地理解结肠IBD的缓解和复发模式，并指导未来炎症发作的治疗和预防。
