2. Academic Validation
  3. Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

  • Cell Mol Immunol. 2021 Jun;18(6):1489-1502. doi: 10.1038/s41423-019-0346-6.
Lu Shi  # 1 2,  Hongling Tian  # 1 2,  Peng Wang  # 1 2,  Ling Li  # 1 2,  Zhaoqi Zhang 1 2,  Jiayu Zhang 1 2,  Yong Zhao 3 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. zhaoy@ioz.ac.cn.
  • 4 University of Chinese Academy of Sciences, Beijing, China. zhaoy@ioz.ac.cn.
  • 5 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. zhaoy@ioz.ac.cn.
  • # Contributed equally.
PMID: 31900461 DOI: 10.1038/s41423-019-0346-6
Abstract

Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified Ras/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

Keywords

Hematopoietic progenitor cells; Macrophage differentiation; Macrophage polarization; Microgravity; RAS/ERK/NFκB pathway.

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