Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorEvrard, Maximilien
dc.identifier.citationEvrard, M. (2017). The role of the CXCL12/CXCR4 axis in monocyte tissue compartmentalisation and homeostasis. Doctoral thesis, Nanyang Technological University, Singapore.
dc.description.abstractMonocytes are integral to innate immune responses against microbial and sterile tissue injury. However, mechanisms that regulate their compartmentalisation in distinct tissues and their rapid mobilisation following inflammatory signals remain poorly understood. Using bone marrow (BM) intravital imaging and BrdU pulsing assays, we found that while all monocytes respond to mobilisation cues, only a minority is able to enter the peripheral circulation, suggesting a heterogeneity among monocytes. Using computational analysis approaches to interpret multi- dimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature and mobilisable CXCR4lo monocytes. We propose that the CXCR4hi subset represents a "transitional pre-monocyte" population and this sequential step of maturation 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, homing to BM and splenic reservoirs and pulmonary margination. Importantly, we showed that reduced monocyte margination through CXCR4 inhibition resulted in decreased occurrence of lung injury and mortality in mouse models of sepsis. Altogether, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.en_US
dc.format.extent189 p.en_US
dc.subjectDRNTU::Science::Biological sciencesen_US
dc.titleThe role of the CXCL12/CXCR4 axis in monocyte tissue compartmentalisation and homeostasisen_US
dc.contributor.supervisorNg Lai Guanen_US
dc.contributor.schoolSchool of Biological Sciencesen_US​Doctor of Philosophy (SBS)en_US
item.fulltextWith Fulltext-
Appears in Collections:SBS Theses
Files in This Item:
File Description SizeFormat 
1_Max_Evrard_PhD_revised final.pdf24.03 MBAdobe PDFThumbnail

Page view(s) 20

checked on Oct 24, 2020

Download(s) 20

checked on Oct 24, 2020

Google ScholarTM


Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.