Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
Front Immunol. 2023 Mar 13;14:1115552. doi: 10.3389/fimmu.2023.1115552. eCollection 2023.
Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn's disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.
作为小肠的守护者，潘氏细胞（Paneth cells，PCs）在维持肠道内稳态中发挥着重要作用。尽管 PCs 仅在肠道内的内稳态下独特存在，但它们的功能障碍不仅涉及肠道疾病，还涉及肠道外器官的各种疾病，这表明 PCs 具有全身性的重要性。PCs 参与这些疾病的机制也是多种多样的。PCs 的参与主要表现为限制坏死性小肠结肠炎、肝病、急性胰腺炎和移植物抗宿主病中的肠道细菌易位。PCs 中的风险基因使肠道易患克罗恩病。在肠道感染中，不同的病原体在 PCs 中诱导不同的反应，细菌表面的 toll 样受体配体触发 PCs 的脱颗粒。肥胖症中胆汁酸水平的显著升高严重损害了 PCs。PCs 可以抑制病毒进入并促进肠道再生，从而缓解 COVID-19。相反，PCs 中丰富的白细胞介素 17A 加重了缺血/再灌注引起的多器官损伤。PCs 的促血管生成作用加重了门静脉高压的严重程度。针对 PCs 的治疗策略主要包括 PC 保护、PC 衍生的炎症细胞因子消除和 AMP 替代治疗。在这篇综述中，我们讨论了迄今为止报道的 PCs 对肠道和肠道外疾病的影响和重要性，以及针对 PCs 的潜在治疗策略。
