Anhui Medical University, Hefei, Anhui, China; Laboratory of Mucosal Barrier Pathophysiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Laboratory of Mucosal Barrier Pathophysiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Cell Mol Gastroenterol Hepatol. 2020;10(2):327-340. doi: 10.1016/j.jcmgh.2020.04.001. Epub 2020 Apr 15.
Defective epithelial barrier function is present in maladies including epidermal burn injury, environmental lung damage, renal tubular disease, and a range of immune-mediated and infectious intestinal disorders. When the epithelial surface is intact, the paracellular pathway between cells is sealed by the tight junction. However, permeability of tight junctions varies widely across tissues and can be markedly impacted by disease. For example, tight junctions within the skin and urinary bladder are largely impermeant and their permeability is not regulated. In contrast, tight junctions of the proximal renal tubule and intestine are selectively permeable to water and solutes on the basis of their biophysical characteristics and, in the gut, can be regulated by the immune system with remarkable specificity. Conversely, modulation of tight junction barrier conductance, especially within the gastrointestinal tract, can impact immune homeostasis and diverse pathologies. Thus, tight junctions are both effectors and targets of immune regulation. Using the gastrointestinal tract as an example, this review explores current understanding of this complex interplay between tight junctions and immunity.
上皮屏障功能缺陷存在于多种疾病中，包括表皮烧伤、环境肺损伤、肾小管疾病以及一系列免疫介导和感染性肠道疾病。当上皮表面完整时，细胞间的旁细胞途径被紧密连接封闭。然而，紧密连接的通透性在组织间差异很大，并且可能受到疾病的显著影响。例如，皮肤和膀胱中的紧密连接基本不可渗透，其通透性不受调节。相比之下，近端肾小管和肠道的紧密连接根据其物理特性对水和溶质具有选择性通透性，并且在肠道中可以通过免疫系统进行显著特异性调节。相反，紧密连接屏障电导的调节，特别是在胃肠道中，可以影响免疫稳态和多种病理。因此，紧密连接既是免疫调节的效应器又是靶标。本文以胃肠道为例，探讨了目前对紧密连接和免疫之间这种复杂相互作用的理解。
