Exosomes Represent an Immune Suppressive T Cell Checkpoint in Human Chronic Inflammatory Microenvironments.
Exosomes Represent an Immune Suppressive T Cell Checkpoint in Human Chronic Inflammatory Microenvironments.
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DOI：
10.1080/08820139.2020.1748047
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发表时间：
2020-10
影响因子：
2.8
通讯作者：
Bankert RB
中科院分区：
文献类型：
--
作者：
Shenoy GN;Bhatta M;Loyall JL;Kelleher RJ Jr;Bernstein JM;Bankert RB
存在于慢性炎性组织如鼻息肉（来自慢性鼻窦炎患者）中的T细胞已被证明对经由TCR的激活低应答，类似于多种不同人类肿瘤微环境中的肿瘤特异性T细胞。虽然已知免疫抑制性外泌体导致肿瘤相关T细胞无法对激活刺激做出最佳反应，但尚不清楚它们是否在慢性炎症微环境中发挥类似作用。在目前的研究中，我们研究了来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、抗体阵列和流式细胞仪通过大小和组成进行表征。外泌体的免疫抑制能力通过量化其对T细胞活化的作用来测量，使用NFκB的核转位作为活化终点。从两种不同类型的人慢性炎症组织-慢性鼻窦炎患者的鼻息肉和类风湿性关节炎患者的滑液中分离和表征外来体。这些外泌体阻止了通过TCR刺激的T细胞的活化。这种免疫抑制，就像在肿瘤微环境中看到的那样，部分依赖于脂质，神经节苷脂GD 3，其在外泌体表面上表达。存在于非恶性慢性炎症组织中的免疫抑制性外泌体代表了一种新的T细胞检查点，并可能代表一种新的治疗靶点，以增强对当前疗法的反应并预防疾病复发。
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 human 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 nonmalignant 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.
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影响因子：
7.4
作者：
Lässer C;O'Neil SE;Shelke GV;Sihlbom C;Hansson SF;Gho YS;Lundbäck B;Lötvall J
通讯作者：
Lötvall J
影响因子：
15.9
作者：
Agrawal, S;Marquet, J;Farcet, JP
通讯作者：
Farcet, JP
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
影响因子：
10.1
作者：
Kelleher RJ Jr;Balu-Iyer S;Loyall J;Sacca AJ;Shenoy GN;Peng P;Iyer V;Fathallah AM;Berenson CS;Wallace PK;Tario J;Odunsi K;Bankert RB
通讯作者：
Bankert RB
影响因子：
3.6
作者：
Dagur, Pradeep K.;Sharma, Bhawna;Joshi, Beenu
通讯作者：
Joshi, Beenu