Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States.
Front Immunol. 2024 May 30;15:1403150. doi: 10.3389/fimmu.2024.1403150. eCollection 2024.
The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered-a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.
髓系细胞与 T 淋巴细胞之间的相互作用对于宿主防御和炎症消退的调节至关重要。这种相互作用的失调可能导致慢性炎症性疾病的发展。在这些疾病中，重要的是动脉粥样硬化，它是指由载脂蛋白 B 含量高的脂蛋白（尤其是低密度脂蛋白，LDL）驱动的动脉内膜局灶性病变，其特征是形成由炎症免疫细胞组成的斑块，收集死细胞和脂质的坏死核心，以及纤维帽。随着疾病的进展，坏死核心扩大，纤维帽变薄，这增加了斑块破裂或侵蚀的风险。斑块破裂导致快速的血栓反应，可能导致心脏病发作、中风或猝死。然而，随着循环 LDL 的显著降低，斑块变得更加稳定，心脏风险降低——这一过程称为动脉粥样硬化消退。动脉粥样硬化进展和消退的一个关键方面是先天（髓系细胞）和适应性（T 淋巴细胞）免疫细胞之间的串扰。髓系细胞专门通过称为吞噬作用的过程清除凋亡细胞，这对于炎症消退是必要的。在晚期疾病中，吞噬作用受损，导致凋亡细胞的继发性坏死、炎症，最重要的是，组织修复缺陷。在消退中，吞噬作用被重新唤醒，有助于炎症消退和斑块稳定。在这里，我们将探讨吞噬作用的髓系细胞如何通过抗原呈递、分泌因子和细胞-细胞接触影响 T 细胞功能，反之亦然，以及这种细胞串扰如何促进动脉粥样硬化的进展或消退。
