Article, see p 1920

Pulmonary arterial hypertension (PAH) is a deleterious disease of the lung vasculature characterized by endothelial dysfunction, medial hypertrophy and proliferation, and eventual occlusion of the pulmonary arterioles. Although a number of genetic and environmental triggers have been described as causative, the specific molecular origins of this vascular disease are still unknown.

Multiple lines of evidence now converge to connect immune dysregulation to PAH in humans and animal models. Previous reports suggest that altered inflammatory dynamics, such as hematopoietic and myeloid expansion, B- and T-cell dysfunction, increased cytokine production, circulating autoantibodies, and tertiary lymphoid tissue neogenesis, may initiate or drive PAH.¹ Clinically, a well-established causative link exists between autoimmune connective tissue disorders and PAH. Furthermore, infectious agents, such as Schistosoma mansoni and human immunodeficiency virus (HIV), are known to alter the immune cell repertoire and predispose to the development of PAH. However, a mechanistic understanding of the exogenous or endogenous factors that drive immune dysfunction remains largely undefined.

Prior studies have aimed to characterize the role of exogenous viruses in PAH. For example, HIV-associated PAH has been attributed to decreased CD4+ T-cell function, indicating a role for T-cell–mediated immune dysregulation.² Separately, HIV-encoded proteins such …

文章，请参见第1920页

肺动脉高压（PAH）是一种肺血管系统的有害疾病，其特征在于内皮功能障碍，内侧肥大和增生以及最终阻塞了肺小动脉。尽管已将多种遗传和环境诱因描述为病因，但该血管疾病的具体分子起源仍是未知的。

现在，在人类和动物模型中，有多种证据可以证明免疫失调与PAH有关联。先前的报告表明，改变的炎症动力学，例如造血和髓样扩张，B细胞和T细胞功能障碍，细胞因子产生增加，循环中的自身抗体以及第三类淋巴组织新生，可能会引发或驱动PAH。¹临床上，自身免疫性结缔组织疾病与PAH之间存在公认的因果关系。此外，传染病，如曼氏血吸虫已知人类免疫缺陷病毒（HIV）和人免疫缺陷病毒（HIV）会改变免疫细胞库，并易患PAH。但是，对驱动免疫功能障碍的外源性或内源性因素的机械理解仍很不确定。

先前的研究旨在表征外源性病毒在PAH中的作用。例如，与HIV相关的PAH归因于CD4 + T细胞功能的降低，表明T细胞介导的免疫失调的作用。²另外，HIV编码的蛋白质，例如……