期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 6, 页码 1489-1502出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-019-0346-6
关键词
Microgravity; Hematopoietic progenitor cells; Macrophage differentiation; Macrophage polarization; RAS; ERK; NF kappa B pathway
类别
资金
- National Key Research and Development Program of China [2017YFA0105002, 2017YFA0104402]
- National Natural Science Foundation of China [U1738111]
- China Manned Space Flight Technology Project [TZ-1]
- National Natural Science Foundation Youth Fund [31800741]
The study shows that spaceflight or simulated microgravity significantly reduces the quantity, function, and differentiation of macrophages, leading to metabolic reprogramming. Additionally, it was found that microgravity regulates macrophage differentiation through the RAS/ERK/NF kappa B and p53 pathways.
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/NF kappa B as a major microgravity-regulated pathway. Exogenous ERK and NF kappa B 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.
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