Key Points Osteopontin promotes homeostasis of mouse and human IEL, mediated by its ligand CD44. iCD8α cells produce osteopontin, which impacts the survival of other IEL. Lack of osteopontin renders mice susceptible to intestinal inflammation. Intestinal intraepithelial lymphocytes (IEL) comprise a diverse population of cells residing in the epithelium at the interface between the intestinal lumen and the sterile environment of the lamina propria. Because of this anatomical location, IEL are considered critical components of intestinal immune responses. Indeed, IEL are involved in many different immunological processes, ranging from pathogen control to tissue stability. However, despite their critical importance in mucosal immune responses, very little is known about the homeostasis of different IEL subpopulations. The phosphoprotein osteopontin is important for critical physiological processes, including cellular immune responses, such as survival of Th17 cells and homeostasis of NK cells among others. Because of its impact in the immune system, we investigated the role of osteopontin in the homeostasis of IEL. In this study, we report that mice deficient in the expression of osteopontin exhibit reduced numbers of the IEL subpopulations TCRγδ+, TCRβ+CD4+, TCRβ+CD4+CD8α+, and TCRβ+CD8αα+ cells in comparison with wild-type mice. For some IEL subpopulations, the decrease in cell numbers could be attributed to apoptosis and reduced cell division. Moreover, we show in vitro that exogenous osteopontin stimulates the survival of murine IEL subpopulations and unfractionated IEL derived from human intestines, an effect mediated by CD44, a known osteopontin receptor. We also show that iCD8α IEL but not TCRγδ+ IEL, TCRβ+ IEL, or intestinal epithelial cells, can promote survival of different IEL populations via osteopontin, indicating an important role for iCD8α cells in the homeostasis of IEL.

中文翻译：

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骨桥蛋白和 iCD8α 细胞促进肠道上皮内淋巴细胞稳态

关键点骨桥蛋白促进小鼠和人 IEL 的稳态，由其配体 CD44 介导。iCD8α 细胞产生骨桥蛋白，影响其他 IEL 的存活。缺乏骨桥蛋白使小鼠容易发生肠道炎症。肠上皮内淋巴细胞 (IEL) 包括位于肠腔和固有层无菌环境之间界面处的上皮细胞中的多种细胞。由于这种解剖位置，IEL 被认为是肠道免疫反应的关键组成部分。事实上，IEL 涉及许多不同的免疫过程，从病原体控制到组织稳定性。然而，尽管它们在粘膜免疫反应中至关重要，但对不同 IEL 亚群的稳态知之甚少。磷蛋白骨桥蛋白对关键生理过程很重要，包括细胞免疫反应，如 Th17 细胞的存活和 NK 细胞的稳态等。由于其对免疫系统的影响，我们研究了骨桥蛋白在 IEL 稳态中的作用。在这项研究中，我们报告说，与野生型小鼠相比，骨桥蛋白表达缺陷的小鼠的 IEL 亚群 TCRγδ+、TCRβ+CD4+、TCRβ+CD4+CD8α+ 和 TCRβ+CD8αα+ 细胞数量减少。对于一些 IEL 亚群，细胞数量的减少可能归因于细胞凋亡和细胞分裂减少。此外，我们在体外显示外源性骨桥蛋白刺激小鼠 IEL 亚群和源自人类肠道的未分级 IEL 的存活，这种作用由 CD44（一种已知的骨桥蛋白受​​体）介导。