2. Academic Validation
  3. A2AR limits IL-15-induced generation of CD39+ NK cells with high cytotoxicity

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

  • Int Immunopharmacol. 2022 Dec 16;114:109567. doi: 10.1016/j.intimp.2022.109567.
Guijie Kang 1,  Xueqin Zhao 1,  Jiafeng Sun 2,  Chen Cheng 1,  Cen Wang 1,  Longxiang Tao 3,  Lu Zong 4,  Wenwei Yin 5,  Jingjing Cong 6,  Jing Li 7,  Xuefu Wang 8
Affiliations

Affiliations

  • 1 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China.
  • 2 Dental Department, Health Service Center, Jianghai Community, Guangyi Street, Liangxi District, Wuxi 214000, Jiangsu, China.
  • 3 Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China.
  • 4 Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China.
  • 5 Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
  • 6 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China. Electronic address: congjingjing@ahmu.edu.cn.
  • 7 School of Life Sciences, Anhui Medical University, Hefei 230032, China. Electronic address: lijing1812@ahmu.edu.cn.
  • 8 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China. Electronic address: wangxuefu@ahmu.edu.cn.
PMID: 36529024 DOI: 10.1016/j.intimp.2022.109567
Abstract

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-γ and TNF-α, relative to CD39- NK cells. Importantly, IL-15 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.

Keywords

A2A adenosine receptor; CD39; Cytotoxicity; IL-15; NK cells.

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