Ryan M Brown, Helen H Le, Isaac W Babcock, Tajie H Harris, Alban Gaultier
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引用次数: 0
Abstract
The Enteric Nervous System is composed of a vastly interconnected network of neurons and glial cells that coordinate to regulate homeostatic gut function including intestinal motility, nutrient sensing, and mucosal barrier immunity. Enteric Glial Cells (EGCs) are a heterogeneous cell population located throughout the gastrointestinal tract and have well described roles in regulating intestinal immune responses. Enteric Glial Cells have been suggested to act as nonconventional antigen presenting cells via the Major Histocompatibility Complex II (MHC II), though this has not been confirmed functionally. Here, we investigate the capability of EGCs to present antigen on MHC I and MHC II using in vitro antigen presentation assays performed with primary murine EGC cultures. We found that EGCs are capable of functional antigen presentation on MHC I, including antigen cross-presentation, but are not capable of functional antigen presentation on MHC II. We also determined EGC cell surface MHC I and MHC II expression levels by flow cytometry during intestinal inflammation during Dextran Sodium Sulfate-induced colitis or acute Toxoplasma gondii infection. We found that EGCs upregulate MHC I during acute T. gondii infection and induce low-level MHC II expression. These findings suggest that EGCs may be important in the regulation of CD8+ T cell responses via MHC I mediated antigen (cross) presentation but may not be relevant for MHC II-mediated antigen presentation.
肠道神经系统由神经元和神经胶质细胞组成的庞大网络相互连接,它们协调调节肠道的平衡功能,包括肠道运动、营养感应和粘膜屏障免疫。肠神经胶质细胞(EGCs)是遍布整个胃肠道的异质性细胞群,在调节肠道免疫反应方面的作用已得到充分描述。有人认为肠胶质细胞可通过主要组织相容性复合体 II(MHC II)充当非常规抗原呈递细胞,但这一观点尚未得到功能上的证实。在这里,我们使用小鼠肠胶质细胞原代培养物进行体外抗原递呈试验,研究肠胶质细胞在 MHC I 和 MHC II 上递呈抗原的能力。我们发现EGC能够在MHC I上进行功能性抗原呈递,包括抗原交叉呈递,但不能在MHC II上进行功能性抗原呈递。我们还通过流式细胞术测定了EGC细胞表面MHC I和MHC II在葡聚糖硫酸钠诱导的结肠炎或急性弓形虫感染等肠道炎症期间的表达水平。我们发现,在弓形虫急性感染期间,EGCs 会上调 MHC I,并诱导低水平的 MHC II 表达。这些发现表明,EGCs 在通过 MHC I 介导的抗原(交叉)呈递调节 CD8+ T 细胞反应方面可能很重要,但可能与 MHC II 介导的抗原呈递无关。
期刊介绍:
GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.