Tissue hypoxia occurs when local oxygen demand exceeds oxygen supply. In chronic inflammatory conditions such as IBD, the increased oxygen demand by resident and gut-infiltrating immune cells coupled with vascular dysfunction brings about a marked reduction in mucosal oxygen concentrations. To counter the hypoxic challenge and ensure their survival, mucosal cells induce adaptive responses, including the activation of hypoxia-inducible factors (HIFs) and modulation of nuclear factor-κB (NF-κB). Both pathways are tightly regulated by oxygen-sensitive prolyl hydroxylases (PHDs), which therefore represent promising therapeutic targets for IBD. In this Review, we discuss the involvement of mucosal hypoxia and hypoxia-induced signalling in the pathogenesis of IBD and elaborate in detail on the role of HIFs, NF-κB and PHDs in different cell types during intestinal inflammation. We also provide an update on the development of PHD inhibitors and discuss their therapeutic potential in IBD.

当局部需氧量超过供氧量时，就会发生组织缺氧。在诸如IBD之类的慢性炎性疾病中，常驻和肠道浸润免疫细胞对氧气的需求增加，加上血管功能障碍，导致粘膜氧浓度显着降低。为了应对低氧挑战并确保其存活，黏膜细胞诱导适应性反应，包括激活缺氧诱导因子（HIFs）和调节核因子-κB（NF-κB）。氧敏感的脯氨酰羟化酶（PHD）严格调节这两个途径，因此代表了有希望的IBD治疗靶点。在这篇综述中，我们讨论了粘膜缺氧和缺氧诱导的信号传导在IBD发病机理中的作用，并详细阐述了HIF的作用，肠道炎症期间不同细胞类型的NF-κB和PHDs。我们还提供了有关PHD抑制剂开发的最新信息，并讨论了其在IBD中的治疗潜力。