Program in Lung Cell Biology and Translational Research, Division of Pulmonary and Critical Care Medicine, East Carolina University, Greenville, NC, USA.
Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, NY, USA.
Adv Exp Med Biol. 2021;1304:39-52. doi: 10.1007/978-3-030-68748-9_3.
Concepts regarding etiology and pathophysiology of sarcoidosis have changed remarkably within the past 5 years. Sarcoidosis is now viewed as a complex multi-causation disease related to a diverse collection of external environmental or infectious signals. It is generally accepted that the cause of sarcoidosis is unknown. Moreover, concepts of the inflammatory pathway have been modified by the realization that intrinsic genetic factors and innate immunity may modify adaptive immune responses to external triggers. With those potential regulatory pathways in mind, we will attempt to discuss the current understanding of the inflammatory response in sarcoidosis with emphasis on development of pulmonary granulomatous pathology. In that context, we will emphasize that both macrophages and T lymphocytes play key roles, with sometimes overlapping cytokine production (i.e., TNFα and IFN-γ) but also with unique mediators that influence the pathologic picture. Numerous studies have shown that in a sizable number of sarcoidosis patients, granulomas spontaneously resolve, usually within 3 years. Other sarcoidosis patients, however, may develop a chronic granulomatous disease which may subsequently lead to fibrosis. This chapter will outline our current understanding of inflammatory pathways in sarcoidosis which initiate and mediate granulomatous changes or onset of pulmonary fibrosis.
过去 5 年来，有关结节病病因和发病机制的概念发生了重大变化。结节病现在被视为一种与多种外部环境或感染信号相关的复杂多病因疾病。人们普遍认为结节病的病因不明。此外，人们认识到内在遗传因素和先天免疫可能会改变对外部触发因素的适应性免疫反应，这一概念改变了炎症途径的概念。考虑到这些潜在的调节途径，我们将尝试讨论目前对结节病炎症反应的理解，重点是肺部肉芽肿性病理的发展。在这种情况下，我们将强调巨噬细胞和 T 淋巴细胞都起着关键作用，有时会产生重叠的细胞因子（即 TNFα 和 IFN-γ），但也有独特的介质会影响病理图像。许多研究表明，在相当数量的结节病患者中，肉芽肿会自发消退，通常在 3 年内。然而，其他结节病患者可能会发展为慢性肉芽肿性疾病，随后可能导致纤维化。本章将概述我们目前对结节病炎症途径的理解，这些途径引发和介导肉芽肿变化或肺纤维化的发生。
