炎症体
颗粒酶B
颗粒酶
免疫学
CD8型
细胞毒性T细胞
穿孔素
CTL公司*
信号转导衔接蛋白
先天免疫系统
生物
癌症研究
免疫系统
细胞生物学
炎症
信号转导
体外
生物化学
作者
Melody Cheong,Kate H. Gartlan,Jason S. Lee,Siok‐Keen Tey,Ping Zhang,Rachel D. Kuns,Christopher E. Andoniou,José Paulo Martins,Karshing Chang,Vivien R. Sutton,Gregory M. Kelly,Antiopi Varelias,Slavica Vučković,Kate A. Markey,Glen M. Boyle,Mark J. Smyth,Christian Engwerda,Kelli P. A. MacDonald,Joseph A. Trapani,Mariapia A. Degli‐Esposti,Motoko Koyama,Geoffrey R. Hill
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2020-05-22
卷期号:8 (8): 1085-1098
被引量:6
标识
DOI:10.1158/2326-6066.cir-19-0653
摘要
Abstract The adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) is known to facilitate caspase-1 activation, which is essential for innate host immunity via the formation of the inflammasome complex, a multiprotein structure responsible for processing IL1β and IL18 into their active moieties. Here, we demonstrated that ASC-deficient CD8+ T cells failed to induce severe graft-versus-host disease (GVHD) and had impaired capacity for graft rejection and graft-versus-leukemia (GVL) activity. These effects were inflammasome independent because GVHD lethality was not altered in recipients of caspase-1/11–deficient T cells. We also demonstrated that ASC deficiency resulted in a decrease in cytolytic function, with a reduction in granzyme B secretion and CD107a expression by CD8+ T cells. Altogether, our findings highlight that ASC represents an attractive therapeutic target for improving outcomes of clinical transplantation.
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