Department of Pathology, University Hospital, Grenoble, France.
Translational Innovation in Medicine and Complexity, Centre National de la Recherche Scientifique UMR5525, La Tronche, France.
Front Immunol. 2021 Aug 18;12:715724. doi: 10.3389/fimmu.2021.715724. eCollection 2021.
In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to staining, apical epithelial cells produced APRIL, and the secreted product had to migrate all through the stratified surface epithelium to reach basal cells. A similar process also occurred in the less-organized crypt epithelium. Tonsil epithelial cells captured secreted APRIL, thanks to their surface expression of the APRIL coreceptor, either syndecan-1 or -4 depending on their differentiation stage. In the most basal epithelial cells, secreted APRIL accumulated inside secretory lamp-1 vesicles in a polarized manner, facing the sub-epithelium. The tonsil epithelium upregulated APRIL production by apical cells and secretion by basal cells upon Toll-like receptor stimulation. Furthermore, LPS-stimulated epithelial cells sustained PC survival in a secreted APRIL-dependent manner. Taken together, our study shows that the tonsil epithelium responds to pathogen sensing by a polarized secretion of APRIL in the sub-epithelial space, wherein PCs reside.
在扁桃体等黏膜中,产生抗体的浆细胞(PCs)位于上皮下间隙,该区域被认为是 PC 存活的适宜环境。增殖诱导配体(APRIL)是该区域存在的 PCs 的一个关键存活因子。根据 染色,顶端上皮细胞产生 APRIL,分泌产物必须穿过分层的表面上皮迁移到基底细胞。类似的过程也发生在上皮隐窝的组织化程度较低的区域。由于其表面表达 APRIL 核心受体,即 syndecan-1 或 -4(取决于其分化阶段),扁桃体上皮细胞能够捕获分泌的 APRIL。在最基底的上皮细胞中,分泌的 APRIL 以极化的方式在腔内积聚在 Lamp-1 囊泡中,面向上皮下间隙。扁桃体上皮细胞在上皮细胞 TLR 刺激后,通过顶端细胞上调 APRIL 的产生和基底细胞的分泌。此外,LPS 刺激的上皮细胞以 APRIL 依赖性方式维持 PCs 的存活。综上所述,我们的研究表明,扁桃体上皮细胞通过在上皮下间隙中呈极化方式分泌 APRIL 来对病原体感应作出反应,PCs 就位于该间隙中。