白细胞介素21
Janus激酶3
生物
CD16
脱颗粒
细胞生物学
白细胞介素12
淋巴因子激活杀伤细胞
抗体
细胞因子
Fc受体
CD49b
受体
NK-92
免疫系统
细胞毒性T细胞
免疫学
分子生物学
CD3型
T细胞
CD8型
体外
生物化学
作者
Ilwoong Hwang,Tianxiang Zhang,Jeannine M. Scott,Ae Ra Kim,Taehyung Lee,Tejaswi Kakarla,Ahrom Kim,John B. Sunwoo,Sung‐Jin Kim
标识
DOI:10.1093/intimm/dxs080
摘要
Abstract NK cells respond to tumor and virus-infected cells directly through several activation receptors, including natural cytotoxicity receptors, or indirectly through the activating Fc receptor CD16 for antibody-coated cells. Triggering of NK-cell effector functions through these receptors depends on physically associated transmembrane signaling adaptors, such as FcRγ (also known as FcεRIγ) and CD3ζ, both of which have been traditionally believed to be expressed by all mature NK cells. However, we have identified a distinct subset of human NK cells that are deficient for FcRγ expression but express normal levels of CD3ζ. FcRγ-deficient NK cells were readily detectable in about one-third of the healthy individuals examined. The deficiency was confined to the CD56dim population and was due to low FcRγ mRNA. FcRγ-deficient NK cells displayed dramatically reduced expression of the natural cytotoxicity receptors NKp46 and NKp30 but still expressed substantial levels of CD16. Compared to FcRγ-expressing NK cells, FcRγ-deficient NK cells showed poor direct reactivity toward tumor targets as measured by cytokine production and degranulation. Unexpectedly, however, FcRγ-deficient NK cells exhibited significantly more robust responsiveness upon stimulation through CD16, particularly for cytokine production, compared to FcRγ-expressing NK cells. Thus, our study reveals FcRγ-deficient NK cells as a novel subset of human NK cells that have remarkably potent responses toward antibody-coated targets. These findings also illustrate a differential contribution of FcRγ and CD3ζ for the expression and functional activity of their associated receptors.
科研通智能强力驱动
Strongly Powered by AbleSci AI