澳大利亚 QIMR Berghofer医学研究所Christian R. Engwerda小组的最新研究发现，NK细胞颗粒蛋白NKG7调节细胞毒性颗粒的胞吐作用和炎症。该研究于2020年8月24日发表于国际学术期刊《自然-免疫学》杂志。

研究人员发现在多种疾病中，自然杀伤细胞颗粒蛋白7（NKG7）是淋巴细胞颗粒胞吐作用和下游炎症的调节因子。在内脏利什曼病和疟疾（两种主要的寄生虫病）患者中，CD4⁺和CD8⁺ T细胞表达的NKG7蛋白在促进炎症中起着关键作用。

此外，由自然杀伤细胞表达的NKG7对于调控癌症的发生、生长和转移至关重要。NKG7在自然杀伤细胞和CD8⁺ T细胞中的功能与其调节细胞凋亡的能力相关。CD107a转运至细胞表面并杀死靶细胞，而NKG7对于感染后CD4⁺T细胞的活化也有重要影响。

因此，研究人员发现了一种新型的治疗靶点，它在一系列具有免疫功能的免疫细胞中表达但发挥不同的免疫反应。

研究人员表示，免疫调节疗法彻底改变了慢性疾病，特别是癌症的治疗。但是，它们的有效性受到限制，并且需要确定新的治疗靶点。

附：英文原文

Title: The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation

Author: Susanna S. Ng, Fabian De Labastida Rivera, Juming Yan, Dillon Corvino, Indrajit Das, Ping Zhang, Rachel Kuns, Shashi Bhushan Chauhan, Jiajie Hou, Xian-Yang Li, Teija C. M. Frame, Benjamin A. McEnroe, Eilish Moore, Jinrui Na, Jessica A. Engel, Megan S. F. Soon, Bhawana Singh, Andrew J. Kueh, Marco J. Herold, Marcela Montes de Oca, Siddharth Sankar Singh, Patrick T. Bunn, Amy Roman Aguilera, Mika Casey, Matthias Braun, Nazanin Ghazanfari, Shivangi Wani, Yulin Wang, Fiona H. Amante, Chelsea L. Edwards, Ashraful Haque, William C. Dougall, Om Prakash Singh, Alan G. Baxter, Michele W. L. Teng, Alex Loukas, Norelle L. Daly, Nicole Cloonan, Mariapia A. Degli-Esposti, Jude Uzonna, William R. Heath, Tobias Bald, Siok-Keen Tey, Kyohei Nakamura, Geoffrey R. Hill, Rajiv Kumar, Shyam Sundar, Mark J. Smyth, Christian R. Engwerda

Issue&Volume: 2020-08-24

Abstract: Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases. NKG7 expressed by CD4+ and CD8+ T cells played key roles in promoting inflammation during visceral leishmaniasis and malaria—two important parasitic diseases. Additionally, NKG7 expressed by natural killer cells was critical for controlling cancer initiation, growth and metastasis. NKG7 function in natural killer and CD8+ T cells was linked with their ability to regulate the translocation of CD107a to the cell surface and kill cellular targets, while NKG7 also had a major impact on CD4+ T cell activation following infection. Thus, we report a novel therapeutic target expressed on a range of immune cells with functions in different immune responses.

DOI: 10.1038/s41590-020-0758-6

Source: https://www.nature.com/articles/s41590-020-0758-6