CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses.

Autor: Chong SZ; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore Ng_Lai_Guan@immunol.a-star.edu.sg Chong_Shu_Zhen@immunol.a-star.edu.sg., Evrard M; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore.; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Devi S; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Chen J; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Lim JY; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., See P; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Zhang Y; Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Biopolis, 138673 Singapore., Adrover JM; Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain., Lee B; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Tan L; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Li JL; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Liong KH; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Phua C; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Balachander A; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Boey A; Institute of Medical Biology (IMB)-Institute of Molecular and Cell Biology (IMCB) Electron Microscopy Suite, A*STAR (Agency for Science, Technology and Research), Biopolis, 138671 Singapore., Liebl D; Institute of Medical Biology (IMB)-Institute of Molecular and Cell Biology (IMCB) Electron Microscopy Suite, A*STAR (Agency for Science, Technology and Research), Biopolis, 138671 Singapore., Tan SM; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Chan JK; Experimental Fetal Medicine Group, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore.; Department of Reproductive Medicine, KK Women's and Children's Hospital, 229899 Singapore.; Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 169857 Singapore., Balabanian K; INSERM UMR-S996, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Université Paris-Sud, 92140 Clamart, France., Harris JE; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605., Bianchini M; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich 80336, Germany., Weber C; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich 80336, Germany., Duchene J; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich 80336, Germany., Lum J; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Poidinger M; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Chen Q; Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Biopolis, 138673 Singapore., Rénia L; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Wang CI; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Larbi A; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Randolph GJ; Division of Immunobiology, Washington University, St. Louis, MO 63110., Weninger W; Centenary Institute for Cancer Medicine and Cell Biology, Newton, New South Wales 2042, Australia., Looney MR; Department of Medicine and Pathology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143., Krummel MF; Department of Medicine and Pathology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143., Biswas SK; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Ginhoux F; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Hidalgo A; Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich 80336, Germany., Bachelerie F; INSERM UMR-S996, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Université Paris-Sud, 92140 Clamart, France., Ng LG; Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore Ng_Lai_Guan@immunol.a-star.edu.sg Chong_Shu_Zhen@immunol.a-star.edu.sg.; School of Biological Sciences, Nanyang Technological University, 637551 Singapore.
Jazyk: angličtina
Zdroj: The Journal of experimental medicine [J Exp Med] 2016 Oct 17; Vol. 213 (11), pp. 2293-2314. Date of Electronic Publication: 2016 Oct 10.
DOI: 10.1084/jem.20160800
Abstrakt: It is well established that Ly6C hi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6C hi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6C hi monocytes consist of two distinct subpopulations (CXCR4 hi and CXCR4 lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4 hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4 lo monocytes. We propose that the CXCR4 hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.
(© 2016 Chong et al.)
Databáze: MEDLINE