Epithelial barriers are essential to maintain multicellular organisms well compartmentalized and protected from external environment. In the intestine, the epithelial layer orchestrates a dynamic balance between nutrient absorption and prevention of microorganisms, and antigen intrusion. Intestinal barrier function has been shown to be altered in coeliac disease but whether it contributes to the pathogenesis development or if it is merely a phenomenon secondary to the aberrant immune response is still unknown. The tight junction complexes are multiprotein cell-cell adhesions that seal the epithelial intercellular space and regulate the paracellular permeability of ions and solutes. These structures have a fundamental role in epithelial barrier integrity as well as in signaling mechanisms that control epithelial-cell polarization, the formation of apical domains and cellular processes such as cell proliferation, migration, differentiation, and survival. In coeliac disease, the molecular structures and function of tight junctions appear disrupted and are not completely recovered after treatment with gluten-free diet. Moreover, zonulin, the only known physiological regulator of the tight junction permeability, appears augmented in autoimmune conditions associated with TJ dysfunction, including coeliac disease. This chapter will examine recent discoveries about the molecular architecture of tight junctions and their functions. We will discuss how different factors contribute to tight junction disruption and intestinal barrier impairment in coeliac disease. To conclude, new insights into zonulin-driven disruption of tight junction structures and barrier integrity in coeliac disease are presented together with the advancements in novel therapy to treat the barrier defect seen in pathogenesis.

上皮屏障对于维持多细胞生物的良好分区和免受外部环境的影响是必不可少的。在肠道中，上皮层在营养吸收和预防微生物以及抗原入侵之间协调平衡。肠屏障功能已被证明在乳糜泻中发生了改变，但它是否有助于发病机制的发展，或者它是否仅仅是异常免疫反应的继发现象仍然未知。紧密连接复合物是多蛋白细胞-细胞粘附，可密封上皮细胞间隙并调节离子和溶质的细胞旁通透性。这些结构在上皮屏障完整性以及控制上皮细胞极化的信号传导机制中具有重要作用，顶端结构域的形成和细胞过程，如细胞增殖、迁移、分化和存活。在乳糜泻中，紧密连接的分子结构和功能似乎被破坏，并且在用无麸质饮食治疗后不能完全恢复。此外，连蛋白，唯一已知的紧密连接通透性的生理调节剂，在与 TJ 功能障碍相关的自身免疫疾病中出现增强，包括乳糜泻。本章将研究有关紧密连接的分子结构及其功能的最新发现。我们将讨论不同因素如何导致乳糜泻中的紧密连接破坏和肠道屏障受损。总而言之，