Kucuksezer Umut Can, Ozdemir Cevdet, Yazici Duygu, Pat Yagiz, Mitamura Yasutaka, Li Manru, Sun Na, D'Avino Paolo, Bu Xiangting, Zhu Xueyi, Akdis Mubeccel, Nadeau Kari, Ogulur Ismail, Akdis Cezmi A
Aziz Sancar Institute of Experimental Medicine, Department of Immunology, Istanbul University, Istanbul, Turkey.
Institute of Child Health, Department of Pediatric Basic Sciences, Istanbul University, Istanbul, Turkey.
Asia Pac Allergy. 2023 Mar;13(1):28-39. doi: 10.5415/apallergy.0000000000000005. Epub 2023 Apr 28.
It is now longer than half a century, humans, animals, and nature of the world are under the influence of exposure to many newly introduced noxious substances. These exposures are nowadays pushing the borders to be considered as the causative or exacerbating factors for many chronic disorders including allergic, autoimmune/inflammatory, and metabolic diseases. The epithelial linings serve as the outermost body's primary physical, chemical, and immunological barriers against external stimuli. The "epithelial barrier theory" hypothesizes that these diseases are aggravated by an ongoing periepithelial inflammation triggered by exposure to a wide range of epithelial barrier-damaging insults that lead to "epithelitis" and the release of alarmins. A leaky epithelial barrier enables the microbiome's translocation from the periphery to interepithelial and even deeper subepithelial areas together with allergens, toxins, and pollutants. Thereafter, microbial dysbiosis, characterized by colonization of opportunistic pathogen bacteria and loss of the number and biodiversity of commensal bacteria take place. Local inflammation, impaired tissue regeneration, and remodeling characterize the disease. The infiltration of inflammatory cells to affected tissues shows an effort to expulse the tissue invading bacteria, allergens, toxins, and pollutants away from the deep tissues to the surface, representing the "expulsion response." Cells that migrate to other organs from the inflammatory foci may play roles in the exacerbation of various inflammatory diseases in distant organs. The purpose of this review is to highlight and appraise recent opinions and findings on epithelial physiology and its role in the pathogenesis of chronic diseases in view of the epithelial barrier theory.
半个多世纪以来，人类、动物以及世界上的自然环境都受到了许多新引入的有害物质暴露的影响。如今，这些暴露正在突破界限，被视为许多慢性疾病的致病或加重因素，包括过敏性疾病、自身免疫/炎症性疾病和代谢性疾病。上皮组织作为身体最外层的主要物理、化学和免疫屏障，抵御外部刺激。“上皮屏障理论”假设，这些疾病因暴露于多种破坏上皮屏障的损伤因素而引发持续的上皮周围炎症，进而加重，这些损伤会导致“上皮炎”并释放警报素。上皮屏障渗漏会使微生物群连同过敏原、毒素和污染物一起从外周转移到上皮间甚至更深的上皮下区域。此后，会发生以机会致病菌定殖以及共生菌数量和生物多样性丧失为特征的微生物群落失调。疾病的特征是局部炎症、组织再生受损和重塑。炎症细胞浸润到受影响的组织中，试图将侵入组织的细菌、过敏原、毒素和污染物从深部组织排出到表面，这代表了“排出反应”。从炎症病灶迁移到其他器官的细胞可能在远处器官的各种炎症性疾病的加重中起作用。本综述的目的是鉴于上皮屏障理论，突出并评估关于上皮生理学及其在慢性疾病发病机制中的作用的最新观点和研究结果。
