Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Thorax. 2010 Nov;65(11):1016-24. doi: 10.1136/thx.2009.132027. Epub 2010 Sep 29.
Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon γ (IFNγ)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological fluids including bronchoalveolar lavage fluid (BALF) from healthy individuals.
To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis.
BALF exosomes from patients with sarcoidosis (n=36) and healthy controls (n=14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA.
BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNγ and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells.
The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
结节病是一种病因不明的全身性疾病，其特征为肉芽肿形成和干扰素 γ（IFNγ）产生的 T 细胞的存在，这些细胞会导致多个器官（尤其是肺部）发生炎症和组织损伤。外泌体是源自内体的纳米大小的免疫调节囊泡，可由多种细胞释放，也存在于包括支气管肺泡灌洗液（BALF）在内的生理液体中。
研究结节病患者的肺部是否比健康个体富集外泌体，以及它们是否可能有助于发病机制。
通过电子显微镜、流式细胞术、Western blot 分析和质谱比较结节病患者（n=36）和健康对照者（n=14）的 BALF 外泌体。将 BALF 外泌体与自身外周血单核细胞（PBMC）或人支气管上皮细胞系 16HBE14o-孵育。通过 ELISPOT 和 ELISA 测量细胞因子。
与健康个体相比，结节病患者的 BALF 显示出外泌体水平升高。与健康个体相比，患者的外泌体表现出 MHC Ⅰ类和Ⅱ类、四跨膜蛋白 CD9、CD63 和 CD81 以及神经调节蛋白-1 的表达显著升高，这些蛋白已知与癌症进展有关。此外，与健康个体相比，患者的 BALF 外泌体可诱导自身 PBMC 产生显著更高水平的 IFNγ 和白细胞介素（IL）-13，并可刺激上皮细胞产生 IL-8。
这些结果首次表明外泌体在人类肺部疾病中发挥作用，可能有助于结节病炎症的发生和进展。这表明外泌体可能是肺部疾病临床治疗的新潜在靶点。
