1. Academic Validation
  2. 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.
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.

Figures
Products