Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, New York, USA.
Immune Modulatory Therapies LLC , Eden, New York, USA.
Immunol Invest. 2020 Oct;49(7):726-743. doi: 10.1080/08820139.2020.1748047. Epub 2020 Apr 17.
: T cells present in chronic inflammatory tissues such as nasal polyps (from chronic rhinosinusitis patients) have been demonstrated to be hypo-responsive to activation via the TCR, similar to tumor-specific T cells in multiple different human tumor microenvironments. While immunosuppressive exosomes have been known to contribute to the failure of the tumor-associated T cells to respond optimally to activation stimuli, it is not known whether they play a similar role in chronic inflammatory microenvironments. In the current study, we investigate whether exosomes derived from chronic inflammatory microenvironments contribute to the immune suppression of T cells. : Exosomes were isolated by ultracentrifugation and characterized by size and composition using nanoparticle tracking analysis, scanning electron microscopy, antibody arrays and flow exometry. Immunosuppressive ability of the exosomes was measured by quantifying its effect on activation of T cells, using nuclear translocation of NFκB as an activation endpoint. : Exosomes were isolated and characterized from two different types of chronic inflammatory tissues - nasal polyps from chronic rhinosinusitis patients and synovial fluid from rheumatoid arthritis patients. These exosomes arrest the activation of T cells stimulated via the TCR. This immune suppression, like that which is seen in tumor microenvironments, is dependent in part upon a lipid, ganglioside GD3, which is expressed on the exosomal surface. : Immunosuppressive exosomes present in non-malignant chronic inflammatory tissues represent a new T cell checkpoint, and potentially represent a novel therapeutic target to enhance the response to current therapies and prevent disease recurrences.
: 慢性炎症组织（如来自慢性鼻-鼻窦炎患者的鼻息肉）中的 T 细胞已被证明对 TCR 介导的激活反应低下，类似于多种不同人类肿瘤微环境中的肿瘤特异性 T 细胞。虽然已经知道免疫抑制性外泌体有助于肿瘤相关 T 细胞对激活刺激的反应不能最佳发挥，但尚不清楚它们在慢性炎症微环境中是否发挥类似作用。在本研究中，我们研究了源自慢性炎症微环境的外泌体是否有助于 T 细胞的免疫抑制。: 通过超速离心分离外泌体，并使用纳米颗粒跟踪分析、扫描电子显微镜、抗体阵列和流式外差法来表征其大小和组成。通过定量测定其对 T 细胞激活的影响来测量外泌体的免疫抑制能力，使用 NFκB 的核易位作为激活终点。: 从两种不同类型的慢性炎症组织（慢性鼻-鼻窦炎患者的鼻息肉和类风湿关节炎患者的滑液）中分离和表征了外泌体。这些外泌体阻止了 TCR 刺激的 T 细胞的激活。这种免疫抑制作用与肿瘤微环境中所见的相似，部分依赖于外泌体表面表达的脂质神经节苷脂 GD3。: 非恶性慢性炎症组织中存在的免疫抑制性外泌体代表了新的 T 细胞检查点，并可能成为增强对当前治疗反应和预防疾病复发的新的治疗靶点。
