Brown Ryan M, Le Helen H, Babcock Isaac W, Harris Tajie H, Gaultier Alban
Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Glia. 2025 Feb;73(2):291-308. doi: 10.1002/glia.24632. Epub 2024 Nov 4.
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.
肠神经系统由一个庞大的相互连接的神经元和神经胶质细胞网络组成，它们协同调节肠道的稳态功能，包括肠道蠕动、营养感知和黏膜屏障免疫。肠神经胶质细胞（EGCs）是分布于整个胃肠道的异质性细胞群体，在调节肠道免疫反应方面具有明确的作用。尽管尚未在功能上得到证实，但有人提出肠神经胶质细胞可通过主要组织相容性复合体II（MHC II）作为非常规抗原呈递细胞。在这里，我们使用原代小鼠EGC培养物进行的体外抗原呈递试验，研究了EGCs在MHC I和MHC II上呈递抗原的能力。我们发现，EGCs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在葡聚糖硫酸钠诱导的结肠炎或急性弓形虫感染引起的肠道炎症期间EGC细胞表面MHC I和MHC II的表达水平。我们发现，在急性弓形虫感染期间，EGCs上调MHC I并诱导低水平的MHC II表达。这些发现表明，EGCs可能在通过MHC I介导的抗原（交叉）呈递调节CD8 T细胞反应中起重要作用，但可能与MHC II介导的抗原呈递无关。
