Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, United States.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2022 Aug 8;13:946794. doi: 10.3389/fimmu.2022.946794. eCollection 2022.
Endothelial cells (ECs) are central to vascular health but also interact with and regulate the immune system. Changes in endothelial state enable immune cells to migrate into the tissue to facilitate repair and fight infection. ECs modulate the function of immune cells through the expression of adhesion molecules, chemokines, major histocompatibility complex (MHC), and an array of co-stimulatory and inhibitor molecules. These interactions allow ECs to act as antigen presenting cells (APCs) and influence the outcome of immune recognition. This study elucidates how EC microenvironment, vascular cell biology, and immune response are not only connected but interdependent. More specifically, we explored how cell-substratum interactions influence EC antigen presentation and co-stimulation, and how these differences affect allorecognition in animal models of cell transplantation. Investigation of EC state was carried out using RNA sequencing while assessment of the allogeneic response includes measurements of immune cell cytotoxic ability, T cell proliferation, cytokine release, serum antibodies, and histological staining. Differences in substratum led to divergent EC phenotypes which in turn influenced immune response to transplanted cells, both due to the physical barrier of matrix-adhesion and differences in expression of surface markers. ECs grown in 2D on tissue culture plastic or in 3D on collagen scaffolds had significantly different basal levels of MHC expression, co-stimulatory and adhesion molecules. When treated with cytokines to mimic an inflammatory state, ECs did not converge to a single phenotype but rather responded differently based on their substratum. Generally, 3D ECs were more responsive to inflammatory stimuli than 2D ECs. These unique expression patterns measured also influence immune recognition . ECs grown in 2D were more likely to provoke a cytotoxic response while 3D ECs induced T cell proliferation. ECs are uniquely configured to sense not only local flow and mechanical forces but a range of markers related to systemic state, including immune function. ECs interact with immune cells with differing results depending on the environment in which the EC-lymphocyte interaction occurs. Therefore, understanding this relationship is essential to predicting and modifying the outcome of EC-immune interacts. We specifically examined the relationship between EC substratum and allorecognition.
内皮细胞（ECs）是血管健康的核心，但它们也与免疫系统相互作用并调节免疫系统。内皮状态的改变使免疫细胞能够迁移到组织中，促进修复和抗感染。EC 通过表达粘附分子、趋化因子、主要组织相容性复合体（MHC）和一系列共刺激和抑制分子来调节免疫细胞的功能。这些相互作用使 EC 能够充当抗原呈递细胞（APCs）并影响免疫识别的结果。本研究阐明了 EC 微环境、血管细胞生物学和免疫反应不仅相互连接，而且相互依存。更具体地说，我们探讨了细胞-基底相互作用如何影响 EC 的抗原呈递和共刺激，以及这些差异如何影响细胞移植动物模型中的同种异体识别。使用 RNA 测序研究 EC 状态，同时评估同种异体反应包括测量免疫细胞细胞毒性、T 细胞增殖、细胞因子释放、血清抗体和组织学染色。基底的差异导致 EC 表型的不同，进而影响移植细胞的免疫反应，这既是由于基质粘附的物理屏障，也是由于表面标记物表达的差异。在组织培养塑料上 2D 培养或在胶原支架上 3D 培养的 EC 具有显著不同的 MHC 表达、共刺激和粘附分子的基础水平。当用细胞因子处理以模拟炎症状态时，EC 不会收敛到单一表型，而是根据其基底以不同的方式做出反应。一般来说，3D EC 对炎症刺激的反应性高于 2D EC。这些独特的表达模式也影响免疫识别。在 2D 中生长的 EC 更有可能引起细胞毒性反应，而 3D EC 则诱导 T 细胞增殖。EC 被独特地配置为不仅可以感知局部流动和机械力，还可以感知与全身状态相关的一系列标记物，包括免疫功能。EC 与免疫细胞相互作用，其结果因 EC-淋巴细胞相互作用发生的环境而异。因此，了解这种关系对于预测和改变 EC-免疫相互作用的结果至关重要。我们专门研究了 EC 基底与同种异体识别之间的关系。
