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

作　　者：Lu Shi Hongling Tian Peng Wang Ling Li Zhaoqi Zhang Jiayu Zhang Yong Zhao 

机构地区：[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]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing,China

出　　处：《Cellular & Molecular Immunology》2021年第6期1489-1502,共14页中国免疫学杂志（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China(2017YFA0105002,Y.Z.2017YFA0104402,L.L.);Joint Funds of the National Natural Science Foundation of China(U1738111,Y.Z.);the China Manned Space Flight Technology Project(TZ-1);the National Natural Science Foundation Youth Fund(31800741,L.S.).

摘　　要：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.

关 键 词：MICROGRAVITY Hematopoietic progenitor cells Macrophage differentiation Macrophage polarization RAS/ERK/NFκB pathway 

分 类 号：R392[医药卫生—免疫学]