Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China.
Cell Prolif. 2021 Jan;54(1):e12958. doi: 10.1111/cpr.12958. Epub 2020 Nov 11.
Paneth cells (PCs) are located at the base of small intestinal crypts and secrete the α-defensins, human α-defensin 5 (HD-5) and human α-defensin 6 (HD-6) in response to bacterial, cholinergic and other stimuli. The α-defensins are broad-spectrum microbicides that play critical roles in controlling gut microbiota and maintaining intestinal homeostasis. Inflammatory bowel disease, including ulcerative colitis and Crohn's disease (CD), is a complicated autoimmune disorder. The pathogenesis of CD involves genetic factors, environmental factors and microflora. Surprisingly, with regard to genetic factors, many susceptible genes and pathogenic pathways of CD, including nucleotide-binding oligomerization domain 2 (NOD2), autophagy-related 16-like 1 (ATG16L1), immunity-related guanosine triphosphatase family M (IRGM), wingless-related integration site (Wnt), leucine-rich repeat kinase 2 (LRRK2), histone deacetylases (HDACs), caspase-8 (Casp8) and X-box-binding protein-1 (XBP1), are relevant to PCs. As the underlying mechanisms are being unravelled, PCs are identified as the central element of CD pathogenesis, integrating factors among microbiota, intestinal epithelial barrier dysfunction and the immune system. In the present review, we demonstrate how these genes and pathways regulate CD pathogenesis via their action on PCs and what treatment modalities can be applied to deal with these PC-mediated pathogenic processes.
潘氏细胞（Paneth cells，PCs）位于小肠隐窝的底部，在细菌、胆碱能和其他刺激物的作用下分泌α-防御素，包括人α-防御素 5（HD-5）和人α-防御素 6（HD-6）。α-防御素是一种广谱的微生物抑制剂，在控制肠道微生物群和维持肠道内稳态方面发挥着关键作用。炎症性肠病（inflammatory bowel disease，IBD）包括溃疡性结肠炎和克罗恩病（Crohn's disease，CD），是一种复杂的自身免疫性疾病。CD 的发病机制涉及遗传因素、环境因素和微生物群。令人惊讶的是，就遗传因素而言，许多 CD 的易感基因和致病途径，包括核苷酸结合寡聚结构域 2（nucleotide-binding oligomerization domain 2，NOD2）、自噬相关 16 样 1（autophagy-related 16-like 1，ATG16L1）、免疫相关鸟苷三磷酸酶家族 M（immunity-related guanosine triphosphatase family M，IRGM）、无翅型 MMTV 整合位点（wingless-related integration site，Wnt）、富含亮氨酸重复激酶 2（leucine-rich repeat kinase 2，LRRK2）、组蛋白去乙酰化酶（histone deacetylases，HDACs）、半胱天冬酶 8（caspase-8，Casp8）和 X 盒结合蛋白 1（X-box-binding protein-1，XBP1），都与 PCs 有关。随着潜在机制的不断揭示，PCs 被确定为 CD 发病机制的核心因素，整合了微生物群、肠道上皮屏障功能障碍和免疫系统之间的各种因素。在本综述中，我们展示了这些基因和途径如何通过对 PCs 的作用来调节 CD 的发病机制，以及可以应用哪些治疗方法来应对这些由 PCs 介导的致病过程。
