2. Academic Validation
  3. Cadmium biphasically impacts the adaptive immune system via regulating mitochondrial activation of hematopoietic stem cells in mice

Cadmium biphasically impacts the adaptive immune system via regulating mitochondrial activation of hematopoietic stem cells in mice

  • Toxicol Appl Pharmacol. 2025 Feb:495:117216. doi: 10.1016/j.taap.2024.117216.
Yifan Zhao 1,  Chuanxuan Wang 1,  Jun Du 2,  Wei Wang 1,  Jiaojiao Wu 1,  Ting Liu 1,  Peng Xue 1,  Yingzi Ju 1,  Xinyu Hong 3,  Jianheng Zheng 4,  Weidong Qu 1,  Yubin Zhang 5
Affiliations

Affiliations

  • 1 Experimental Center for Research, School of Public Health and Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China.
  • 2 Amway (Shanghai) Innovation & Science Co., Ltd, Shanghai 201203, China.
  • 3 Institute of Chemical Toxicity Testing/State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China. Electronic address: hongxinyu@scdc.sh.cn.
  • 4 Amway (Shanghai) Innovation & Science Co., Ltd, Shanghai 201203, China. Electronic address: jennie.zheng@amway.com.
  • 5 Experimental Center for Research, School of Public Health and Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China. Electronic address: yz001@fudan.edu.cn.
PMID: 39725238 DOI: 10.1016/j.taap.2024.117216
Abstract

Cadmium (Cd) is a highly toxic metal in human body, and therefore understanding the immunotoxicity of Cd is significant for public health. The aim of this study was to investigate the role of hematopoietic stem cells (HSC) in regulating the immunotoxicity of Cd. After exposure to 10 ppm Cd via drinking water for up to 9 months, C57BL/6 mice had a suppressed adaptive immune system at day 135 but had an enhanced adaptive immune system at day 270 during Cd exposure. The biphasic impacts of Cd on the adaptive immune system were correlated to the mitochondrial (MT) activation of HSC. Mechanistically, a direct action of Cd activated the non-canonical Wnt signaling to increase MT activation in HSC in the bone marrow (BM) at day 90, thus resulting in an impaired adaptive immune system in mice at day 135 during Cd exposure; conversely, Cd reduced the production of thrombopoietin (TPO) by osteoblasts in the BM to suppress MT activation in HSC at day 180, which in turn caused an enhanced adaptive immune system in mice at day 270 during Cd exposure. Thus, Cd biphasically impacts the adaptive immune system via regulating MT activation of HSC, providing a novel angle for understanding the immunotoxicology of metals.

Keywords

Adaptive immune system; Cadmium; Hematopoietic stem cells; Mitochondrial activation; Thrombopoietin.

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