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Extracellular ATP Activates the NLRP3 Inflammasome and Is an Early Danger Signal of Skin Allograft Rejection.
Cell Reports ( IF 7.5 ) Pub Date : 2017-Dec-19 , DOI: 10.1016/j.celrep.2017.11.079
Joaquín Amores-Iniesta 1 , Maria Barberà-Cremades 1 , Carlos M Martínez 2 , José A Pons 1 , Beatriz Revilla-Nuin 3 , Laura Martínez-Alarcón 1 , Francesco Di Virgilio 4 , Pascual Parrilla 1 , Alberto Baroja-Mazo 1 , Pablo Pelegrín 1
Cell Reports ( IF 7.5 ) Pub Date : 2017-Dec-19 , DOI: 10.1016/j.celrep.2017.11.079
Joaquín Amores-Iniesta 1 , Maria Barberà-Cremades 1 , Carlos M Martínez 2 , José A Pons 1 , Beatriz Revilla-Nuin 3 , Laura Martínez-Alarcón 1 , Francesco Di Virgilio 4 , Pascual Parrilla 1 , Alberto Baroja-Mazo 1 , Pablo Pelegrín 1
Affiliation
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Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells. In human liver transplant patients undergoing progressive immunosuppressive drug withdrawal, we found that patients experiencing acute rejection had higher levels of the P2X7 receptor in circulating inflammatory monocytes compared to tolerant patients. These data suggest that the pharmacological inhibition of the P2X7 receptor or the NLRP3 inflammasome will aid in inducing transplant tolerance without complete immunoparalysis.
中文翻译：
细胞外 ATP 激活 NLRP3 炎性体，是皮肤同种异体移植排斥的早期危险信号。
免疫细胞配备了许多识别无菌损伤和病原体的受体。我们发现宿主免疫细胞释放 ATP 作为炎症信号以响应同种异体移植。然后 ATP 通过 P2X7 通道上的反馈机制激活 NLRP3 炎症小体，随后处理和释放白细胞介素 (IL)-18。该过程是通过干扰素-γ 产生对抗同种异体移植的有害 Th1 反应的必要阶段。IL-18 的缺乏导致移植物浸润 CD8 细胞减少，但调节性 T 细胞增加。在接受渐进性免疫抑制药物戒断的人肝移植患者中，我们发现与耐受患者相比，经历急性排斥反应的患者循环炎症单核细胞中的 P2X7 受体水平更高。
更新日期：2017-12-20
中文翻译：
细胞外 ATP 激活 NLRP3 炎性体，是皮肤同种异体移植排斥的早期危险信号。
免疫细胞配备了许多识别无菌损伤和病原体的受体。我们发现宿主免疫细胞释放 ATP 作为炎症信号以响应同种异体移植。然后 ATP 通过 P2X7 通道上的反馈机制激活 NLRP3 炎症小体，随后处理和释放白细胞介素 (IL)-18。该过程是通过干扰素-γ 产生对抗同种异体移植的有害 Th1 反应的必要阶段。IL-18 的缺乏导致移植物浸润 CD8 细胞减少，但调节性 T 细胞增加。在接受渐进性免疫抑制药物戒断的人肝移植患者中，我们发现与耐受患者相比，经历急性排斥反应的患者循环炎症单核细胞中的 P2X7 受体水平更高。
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