A2AR limits IL-15-induced generation of CD39+NK cells with high cytotoxicity

作者全名："Kang, Guijie; Zhao, Xueqin; Sun, Jiafeng; Cheng, Chen; Wang, Cen; Tao, Longxiang; Zong, Lu; Yin, Wenwei; Cong, Jingjing; Li, Jing; Wang, Xuefu"

作者地址："[Kang, Guijie; Zhao, Xueqin; Cheng, Chen; Wang, Cen; Cong, Jingjing; Li, Jing; Wang, Xuefu] Anhui Med Univ, Sch Pharm, Inflammat & Immune Mediated Dis Lab Anhui Prov, 1 Meishan Rd, Hefei 230032, Anhui, Peoples R China; [Sun, Jiafeng] Hlth Serv Ctr, Dent Dept, Guangyi St, Wuxi 214000, Jiangsu, Peoples R China; [Tao, Longxiang] Anhui Med Univ, Affiliated Hosp 1, Dept Radiol, Hefei 230032, Anhui, Peoples R China; [Zong, Lu] Anhui Med Univ, Affiliated Hosp 1, Dept Clin Lab, Hefei 230032, Anhui, Peoples R China; [Yin, Wenwei] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Chongqing, Peoples R China; [Li, Jing] Anhui Med Univ, Sch Life Sci, Hefei 230032, Anhui, Peoples R China"

通信作者："Cong, JJ; Li, J; Wang, XF (通讯作者)，Anhui Med Univ, Sch Pharm, Inflammat & Immune Mediated Dis Lab Anhui Prov, 1 Meishan Rd, Hefei 230032, Anhui, Peoples R China."

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000906580700001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：114

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：NK cells; CD39; Cytotoxicity; A2A adenosine receptor; IL-15

摘要："CD39-mediated inhibition of natural killer (NK) cell activity has been demonstrated, but the characteristics of CD39+ NK cells in humans are not known. We investigated the characteristics of human circulating CD39+ NK cells. In healthy donors, the proportion of circulating CD39+ NK cells in total NK cells was relatively low compared with that of CD39- NK cells. Nonetheless, a higher proportion of CD39+ NK cells expressed CD107a. Similarly, a higher proportion of CD39+ NK cells expressed CD107a in patients with hepatitis B virus or patients with hepatocellular carcinoma. Stimulation with NK-sensitive K562 cells or interleukin (IL)-12/IL-18 activated CD39+ NK cells to express higher levels of CD107a, IFN-gamma and TNF-alpha, relative to CD39- NK cells. Importantly, IL15 induced the generation of CD39+ NK cells. In contrast, A2A adenosine receptor (A2AR) ligation suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. These data for the first time demonstrated that A2AR counteracts IL-15-induced generation of human CD39+ NK cells, which have a stronger cytotoxicity than CD39- NK cells. IL-15-induced human CD39+ NK cells might be better choice for immunotherapy based on adoptive transfer of NK cells."

基金机构："Natural Science Foundation of Anhui Province of China [2108085Y28, 2208085Y26]; Synergy Innovation Program of Anhui Province of China [GXXT-2021-039]; Supporting Program for Outstanding Young Talents in Universities of Anhui Province of China [gxyqZD2021103]; Research Improvement Program of Anhui Medical University [2019xkjT007]"

基金资助正文："Publication of this manuscript was supported by the Natural Science Foundation of Anhui Province of China (2108085Y28 and 2208085Y26) , theUniversity Synergy Innovation Program of Anhui Province of China (GXXT-2021-039) , the Supporting Program for Outstanding Young Talents in Universities of Anhui Province of China (gxyqZD2021103) and the Research Improvement Program of Anhui Medical University (2019xkjT007) ."