Tomii Toshihiro, Kano Gen
Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
Department of Pediatrics, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
Front Allergy. 2025 Aug 8;6:1608202. doi: 10.3389/falgy.2025.1608202. eCollection 2025.
Eosinophils (Eos), long recognized for their roles in allergy and helminth defense, are now emerging as key players in gastrointestinal immune regulation. In inflammatory bowel disease (IBD), eosinophils are frequently elevated in both blood and intestinal tissues, yet their functional significance has been underexplored. This review reexamines the role of eosinophils in IBD pathogenesis, integrating recent insights into mucosal immunity and tissue homeostasis. We outline the shift in perspective from viewing eosinophils solely as inflammatory effectors to recognizing their dual roles in inflammation and repair. Clinical and experimental findings reveal correlations between eosinophil abundance, activation markers, granule protein release, and disease activity in IBD. Central to our model is the regulatory function of eosinophil-derived reactive oxygen species (ROS), particularly hydrogen peroxide, in maintaining intestinal barrier integrity. Dysregulation of ROS-due to dysbiosis or genetic variants-may impair healing and exacerbate inflammation. We further highlight Siglec-8, an inhibitory receptor on eosinophils that induces apoptosis in response to Neu5Ac-containing sialic acids. This pathway may be disrupted by Neu5Gc, a non-human sialic acid abundant in red meat, potentially linking Western diets to impaired eosinophil regulation. These findings suggest new therapeutic directions targeting Siglec-8 and ROS balance to modulate eosinophil activity and restore intestinal immune homeostasis in IBD. These insights may also help bridge traditionally distinct disease paradigms by highlighting a potential common pathogenic mechanism of epithelial barrier dysfunction and dysregulated eosinophil activation shared between allergic diseases (e.g., asthma, eosinophilic esophagitis) and IBD.
嗜酸性粒细胞（Eos）长期以来因其在过敏和抗蠕虫防御中的作用而被认可，现在正成为胃肠道免疫调节的关键参与者。在炎症性肠病（IBD）中，嗜酸性粒细胞在血液和肠道组织中经常升高，但其功能意义尚未得到充分探索。这篇综述重新审视了嗜酸性粒细胞在IBD发病机制中的作用，整合了最近对黏膜免疫和组织稳态的见解。我们概述了从仅将嗜酸性粒细胞视为炎症效应器到认识到它们在炎症和修复中的双重作用的观念转变。临床和实验结果揭示了嗜酸性粒细胞丰度、激活标志物、颗粒蛋白释放与IBD疾病活动之间的相关性。我们模型的核心是嗜酸性粒细胞衍生的活性氧（ROS），特别是过氧化氢，在维持肠道屏障完整性方面的调节功能。由于微生物群失调或基因变异导致的ROS失调可能会损害愈合并加剧炎症。我们进一步强调了Siglec-8，这是一种嗜酸性粒细胞上的抑制性受体，可响应含Neu5Ac的唾液酸诱导细胞凋亡。这条途径可能会被红肉中丰富的非人类唾液酸Neu5Gc破坏，这可能将西方饮食与嗜酸性粒细胞调节受损联系起来。这些发现提示了针对Siglec-8和ROS平衡的新治疗方向，以调节嗜酸性粒细胞活性并恢复IBD中的肠道免疫稳态。这些见解还可能有助于弥合传统上不同的疾病范式，通过突出过敏性疾病（如哮喘、嗜酸性粒细胞性食管炎）和IBD之间上皮屏障功能障碍和嗜酸性粒细胞激活失调的潜在共同致病机制。
