The bone-liver interaction modulates immune and hematopoietic function through Pinch-Cxcl12-Mbl2 pathway

Tailin He1; Bo Zhou1; Guohuan Sun2; Qinnan Yan1; Sixiong Lin3; Guixing Ma1; Qing Yao1; Xiaohao Wu1; Yiming Zhong1; Donghao Gan1; Shaochuan Huo4; Wenfei Jin5; Di Chen6; Xiaochun Bai7; Tao Cheng2; Huiling Cao1; Guozhi Xiao1

2023-12-07

10.1038/s41418-023-01243-9

CELL DEATH AND DIFFERENTIATION   影响因子和分区

1350-9047

1476-5403

Mesenchymal stromal cells (MSCs) are used to treat infectious and immune diseases and disorders; however, its mechanism(s) remain incompletely defined. Here we find that bone marrow stromal cells (BMSCs) lacking Pinch1/2 proteins display dramatically reduced ability to suppress lipopolysaccharide (LPS)-induced acute lung injury and dextran sulfate sodium (DSS)-induced inflammatory bowel disease in mice. Prx1-Cre; Pinch1f/f; Pinch2-/- transgenic mice have severe defects in both immune and hematopoietic functions, resulting in premature death, which can be restored by intravenous injection of wild-type BMSCs. Single cell sequencing analyses reveal dramatic alterations in subpopulations of the BMSCs in Pinch mutant mice. Pinch loss in Prx1+ cells blocks differentiation and maturation of hematopoietic cells in the bone marrow and increases production of pro-inflammatory cytokines TNF-alpha and IL-1 beta in monocytes. We find that Pinch is critical for expression of Cxcl12 in BMSCs; reduced production of Cxcl12 protein from Pinch-deficient BMSCs reduces expression of the Mbl2 complement in hepatocytes, thus impairing the innate immunity and thereby contributing to infection and death. Administration of recombinant Mbl2 protein restores the lethality induced by Pinch loss in mice. Collectively, we demonstrate that the novel Pinch-Cxcl12-Mbl2 signaling pathway promotes the interactions between bone and liver to modulate immunity and hematopoiesis and may provide a useful therapeutic target for immune and infectious diseases.

SCI

英语

第一 ; 共同第一 ; 通讯

Southern University of Science and Technology["81991513","82230081","82250710175","82261160395","82004395"] ; National Natural Science Foundation of China[2019YFA0906004] ; National Key Research and Development Program of China[2017B030301018] ; Guangdong Provincial Science and Technology Innovation Council["CYJ20220818100617036","ZDSYS20140509142721429"]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:001119029000001

SPRINGERNATURE

MOLECULAR BIOLOGY & GENETICS

人工提交

1.Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, 518055, China.
2.State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China; CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
3.Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
4.Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
5.Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.
6.Research Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
7.Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

Tailin He,Bo Zhou,Guohuan Sun,et al. The bone-liver interaction modulates immune and hematopoietic function through Pinch-Cxcl12-Mbl2 pathway[J]. CELL DEATH AND DIFFERENTIATION,2023.

Tailin He.,Bo Zhou.,Guohuan Sun.,Qinnan Yan.,Sixiong Lin.,...&Guozhi Xiao.(2023).The bone-liver interaction modulates immune and hematopoietic function through Pinch-Cxcl12-Mbl2 pathway.CELL DEATH AND DIFFERENTIATION.

Tailin He,et al."The bone-liver interaction modulates immune and hematopoietic function through Pinch-Cxcl12-Mbl2 pathway".CELL DEATH AND DIFFERENTIATION (2023).