Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Adv Pharmacol. 2024;101:237-264. doi: 10.1016/bs.apha.2024.10.002. Epub 2024 Oct 16.
Inflammatory bowel disease (IBD) encompasses chronic inflammatory conditions of the distal gastrointestinal tract, including Crohn's disease and ulcerative colitis. This chapter explores the potential of Dendritic cell-associated C-type lectin-1 (Dectin-1), a pattern recognition receptor, as a therapeutic target for IBD. We delve into the multifaceted roles of Dectin-1 in immune response modulation, focusing on its interactions with the gut microbiota and immune system. Key sections include an examination of intestinal dysbiosis and its impact on IBD, highlighting the critical role of fungal dysbiosis and immune responses mediated by Dectin-1. The chapter discusses the dual functions of Dectin-1 in maintaining gut homeostasis and its contribution to disease pathogenesis through interactions with the gut's fungal community. Furthermore, the genetic and molecular mechanisms underpinning Dectin-1's role in IBD susceptibility are explored, alongside its signaling pathways and their effects on immune modulation. We also present therapeutic strategies targeting Dectin-1, including innovative drug delivery systems that leverage its natural binding affinity for β-glucans, enhancing targeted delivery to inflamed tissues. The chapter underscores the potential of dietary modulation of Dectin-1 pathways to restore gut microbiota balance and suggests future research directions to fully exploit Dectin-1's therapeutic potential in managing IBD. By elucidating the complex interplay between Dectin-1 and the gut microbiota, this chapter provides insights into novel therapeutic approaches aimed at mitigating IBD symptoms and improving patient outcomes.
炎症性肠病（IBD）包括远端胃肠道的慢性炎症性疾病，包括克罗恩病和溃疡性结肠炎。本章探讨了树突状细胞相关 C 型凝集素-1（Dectin-1）作为 IBD 治疗靶点的潜力。我们深入研究了 Dectin-1 在免疫反应调节中的多方面作用，重点关注其与肠道微生物群和免疫系统的相互作用。关键部分包括检查肠道菌群失调及其对 IBD 的影响，强调真菌菌群失调和 Dectin-1 介导的免疫反应的关键作用。本章讨论了 Dectin-1 在维持肠道内稳态中的双重功能及其通过与肠道真菌群落相互作用促进疾病发病机制的作用。此外，还探讨了 Dectin-1 在 IBD 易感性中发挥作用的遗传和分子机制，以及其信号通路及其对免疫调节的影响。我们还提出了针对 Dectin-1 的治疗策略，包括利用其对β-葡聚糖的天然结合亲和力的创新药物递送系统，增强对炎症组织的靶向递送。本章强调了通过调节 Dectin-1 途径来恢复肠道微生物群平衡的饮食调节的潜力，并提出了未来的研究方向，以充分利用 Dectin-1 在治疗 IBD 中的治疗潜力。通过阐明 Dectin-1 与肠道微生物群之间的复杂相互作用，本章提供了有关旨在减轻 IBD 症状和改善患者预后的新型治疗方法的见解。
