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紧密连接蛋白在免疫细胞中的表达和定位谱依赖于其激活状态。

Expression and Localization Profiles of Tight Junction Proteins in Immune Cells Depend on Their Activation Status.

机构信息

Clinical Physiology/Nutritional Medicine, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.

Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.

出版信息

Int J Mol Sci. 2024 Apr 29;25(9):4861. doi: 10.3390/ijms25094861.

Abstract

The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after activation. For paracellular migration, interactions with tight junctions (TJs) are necessary, and previous studies reported TJ protein expression in several immune cells. Our investigation aimed to characterize, in more detail, the expression profiles of TJ proteins in different immune cells in both naïve and activated states. The mRNA expression analysis revealed distinct expression patterns for TJ proteins, with notable changes, mainly increases, upon activation. At the protein level, LSR appeared predominant, being constitutively present in naïve cell membranes, suggesting roles as a crucial interaction partner. Binding experiments suggested the presence of claudins in the membrane only after stimulation, and claudin-8 translocation to the membrane occurred after stimulation. Our findings suggest a dynamic TJ protein expression in immune cells, implicating diverse functions in response to stimulation, like interaction with TJ proteins or regulatory roles. While further analysis is needed to elucidate the precise roles of TJ proteins, our findings indicate important non-canonical functions of TJ proteins in immune response.

摘要

免疫系统对抗病原体的能力依赖于一些过程,如树突状细胞和巨噬细胞通过内皮层和上皮层进行抗原采样,或用树突穿透它们。此外,其他免疫细胞亚型在激活后也会通过上皮层迁移。对于细胞旁迁移,与紧密连接(TJ)的相互作用是必要的,先前的研究报告了几种免疫细胞中的 TJ 蛋白表达。我们的研究旨在更详细地描述在未激活和激活状态下不同免疫细胞中 TJ 蛋白的表达谱。mRNA 表达分析显示 TJ 蛋白的表达模式明显不同,主要在激活后增加。在蛋白质水平上,LSR 似乎占主导地位,在未激活的细胞膜中持续存在,表明其作为关键相互作用伙伴的作用。结合实验表明,只有在刺激后,膜中才存在紧密连接蛋白,并且刺激后紧密连接蛋白-8 向膜转移。我们的发现表明免疫细胞中 TJ 蛋白的表达具有动态性,暗示了在刺激反应中具有多种功能,如与 TJ 蛋白相互作用或调节作用。虽然需要进一步分析来阐明 TJ 蛋白的确切作用,但我们的发现表明 TJ 蛋白在免疫反应中具有重要的非典型功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b0f/11084252/e36fd80aa5a0/ijms-25-04861-g001.jpg

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