Histone deacetylase 9 deficiency exaggerates uterine M2 macrophage polarization

被引:20
作者
Liu, Yanqin [1 ,2 ,3 ,4 ]
Du, Meirong [5 ]
Lin, Hai-Yan [1 ,6 ,7 ]
机构
[1] Chinese Acad Sci, Inst Zool, State Key Lab Stern Cell & Reprod Biol, Beijing 100101, Peoples R China
[2] Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Peoples R China
[3] Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China
[4] Nankai Univ, Coll Life Sci, Tianjin, Peoples R China
[5] Fudan Univ, Gynecol & Obstet Hosp, Shanghai, Peoples R China
[6] Chinese Acad Sci, Inst Zool, Key Lab Zool Systemat & Evolut, Beijing 100101, Peoples R China
[7] Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China
基金
北京市自然科学基金; 中国国家自然科学基金;
关键词
abortion; histone deacetylase 9; macrophage polarization; pregnancy; uterine macrophage; REGULATORY T-CELLS; ADOPTIVE TRANSFER; INFLAMMATORY RESPONSES; DECIDUAL MACROPHAGES; DENDRITIC CELLS; PRONE MICE; M1; INHIBITORS; PROMOTES; CANCER;
D O I
10.1111/jcmm.16616
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The maternal-foetal interface is an immune-privileged site where the semi-allogeneic embryo is protected from attacks by the maternal immune system. Uterine macrophages are key players in establishing and maintaining pregnancy, and the dysregulation of the M1-M2 subpopulation balance causes abortion. We separated two distinct mouse uterine macrophage subpopulations during early pregnancy, CD45(+)F4/80(+)CD206(-) M1-like (M1) and CD45(+)F4/80(+)CD206(+) M2-like (M2) cells. The M1 preponderance was significantly exaggerated at 6 hours after lipopolysaccharide (LPS) treatment, and adoptive transfer of M2 macrophages partially rescued LPS-induced abortion. RNA sequencing analysis of mouse uterine M2 versus M1 revealed 1837 differentially expressed genes (DEGs), among which 629 was up-regulated and 1208 was down-regulated. Histone deacetylase 9 (Hdac9) was one of the DEGs and validated to be significantly up-regulated in uterine M2 as compared with M1. Remarkably, this differential expression profile between M1 and M2 was also evident in primary splenic macrophages and in vitro polarized murine peritoneal, bone marrow-derived and RAW 264.7 macrophages. In Hdac9/HDAC9 knockout RAW 264.7 and human THP-1-derived macrophages, the expression of M1 differentiation markers was unchanged or decreased whereas M2 markers were increased compared with the wild-type cells, and these effects were unrelated to compromised proliferation. Furthermore, Hdac9/HDAC9 ablation significantly enhanced the phagocytosis of fluorescent microspheres in M2 Raw 264.7 cells yet decreased the capacity of THP-1-derived M1 macrophages. The above results demonstrate that Hdac9/HDAC9 deficiency exaggerates M2 macrophage polarization in mouse and human macrophages, which may provide clues for our understanding of the epigenetic regulation on macrophage M1/M2 polarization in maternal-foetal tolerance.
引用
收藏
页码:7690 / 7708
页数:19
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