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 Lu Shi;Hongling Tian;Peng Wang;Ling Li;Zhaoqi Zhang;Jiayu Zhang;Yong Zhao

作者机构：State Key Laboratory of Membrane BiologyInstitute of ZoologyChinese Academy of SciencesBeijingChina University of Chinese Academy of SciencesBeijingChina Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2021年第18卷第6期

页      面：1489-1502页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

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.) 

主　　题：Microgravity Hematopoietic progenitor cells Macrophage differentiation Macrophage polarization RAS/ERK/NFκB pathway 

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.