炎症与肠屏障：白细胞-上皮细胞相互作用、细胞连接重塑与黏膜修复
2016年10月，美国胃肠病学会研究所官方期刊《胃肠病学》正式发表密歇根大学医学院病理学家的综述《炎症与肠屏障：白细胞-上皮细胞相互作用、细胞连接重塑与黏膜修复》。
肠道由单层柱状上皮细胞所被覆，并形成一个动态的渗透性屏障，参与营养物质的选择性吸收，同时限制人体对病原体和食源性抗原的吸收。因此，精确调节上皮屏障功能对于维持黏膜内环境稳态尤为必要，这种调节作用部分取决于上皮屏障的构成以及黏膜促炎因子与抗炎因子间的平衡。在炎症性肠病等病理状态下，肠上皮渗透性增加，从而导致微生物抗原过度暴露，白细胞募集，可溶性介质释放，最终导致肠黏膜受损。炎性微环境通过直接和间接途径，改变上皮细胞间连接的结构和功能，影响上皮屏障性能和黏膜内稳态。我们综述了目前所了解的肠上皮和免疫细胞间复杂的相互作用，重点关注病理性黏膜炎症和上皮修复的机制；同时讨论了白细胞-上皮间相互作用，以及影响上皮屏障和黏膜修复的炎症介质。提高对上皮细胞和免疫系统间网状相互作用的认识，有助于建立组织特异性策略以治疗病理性肠道炎症。
Gastroenterology. 2016 Oct;151(4):616-32.
Inflammation and the Intestinal Barrier: Leukocyte-Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair.
Luissint AC, Parkos CA, Nusrat A.
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.
The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte-epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation.
KEYWORDS: Epithelium; Inflammation; Mucosal Barrier; Mucosal Repair
PMID: 27436072
DOI: 10.1053/j.gastro.2016.07.008