PMID- 26473398 OWN - NLM STAT- MEDLINE DCOM- 20160510 LR - 20220129 IS - 1527-3350 (Electronic) IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 63 IP - 1 DP - 2016 Jan TI - Bidirectional transendothelial migration of monocytes across hepatic sinusoidal endothelium shapes monocyte differentiation and regulates the balance between immunity and tolerance in liver. PG - 233-46 LID - 10.1002/hep.28285 [doi] AB - Monocytes are versatile cells that can fulfill proinflammatory and anti-inflammatory functions when recruited to the liver. Recruited monocytes differentiate into tissue macrophages and dendritic cells, which sample antigens and migrate to lymph nodes to elicit T-cell responses. The signals that determine monocyte differentiation and the role of hepatic sinusoidal endothelial cells (HSECs) in this process are poorly understood. HSECs are known to modulate T-cell activation, which led us to investigate whether transendothelial migration of monocytes across HSECs influences their phenotype and function. Subsets of blood-derived monocytes were allowed to transmigrate across human HSECs into a collagen matrix. Most migrated cells remained in the subendothelial matrix, but ~10% underwent spontaneous basal to apical transendothelial migration. The maturation, cytokine secretion, and T-cell stimulatory capacity of reverse transmigrating (RT) and subendothelial (SE) monocytes were compared. SE monocytes were mainly CD16(-) , whereas 75%-80% of RT monocytes were CD16(+) . SE monocytes derived from the CD14(++) CD16(-) subset and exhibited high phagocytic activity, whereas RT monocytes originated from CD14(++) CD16(+) and CD14(+) CD16(++) monocytes, displayed an immature dendritic cell-like phenotype (CD11c(pos) HLA-DR(pos) CD80lo CD86lo ), and expressed higher levels of chemokine (C-C motif) receptor 8. Consistent with a dendritic cell phenotype, RT monocytes secreted inflammatory cytokines and induced antigen-specific CD4(+) T-cell activation. In contrast, SE monocytes suppressed T-cell proliferation and activation and exhibited endotoxin tolerance. Transcriptome analysis underscored the functional differences between SE and RT monocytes. CONCLUSIONS: Migration across HSECs shapes the subsequent fate of monocytes, giving rise to anergic macrophage-like cells in tissue and the release of immunocompetent pre-dendritic cells into the circulation. CI - (c) 2015 by the American Association for the Study of Liver Diseases. FAU - Zimmermann, Henning W AU - Zimmermann HW AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. AD - Department of Medicine III, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. FAU - Bruns, Tony AU - Bruns T AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. AD - Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany. AD - Center for Sepsis Control and Care, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany. FAU - Weston, Chris J AU - Weston CJ AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. FAU - Curbishley, Stuart M AU - Curbishley SM AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. FAU - Liaskou, Evaggelia AU - Liaskou E AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. FAU - Li, Ka-Kit AU - Li KK AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. FAU - Resheq, Yazid J AU - Resheq YJ AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. AD - Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany. FAU - Badenhorst, Paul W AU - Badenhorst PW AD - School of Immunity and Infection, University of Birmingham, Birmingham, UK. FAU - Adams, David H AU - Adams DH AD - National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. LA - eng GR - Wellcome Trust/United Kingdom GR - G0700301/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151123 PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 SB - IM MH - *Cell Differentiation MH - Cells, Cultured MH - Endothelium/cytology MH - Humans MH - *Immune Tolerance MH - Liver/*cytology/*immunology MH - Monocytes/*physiology MH - Transendothelial and Transepithelial Migration/*physiology PMC - PMC6016741 MID - EMS78107 EDAT- 2015/10/17 06:00 MHDA- 2016/05/11 06:00 PMCR- 2018/06/25 CRDT- 2015/10/17 06:00 PHST- 2015/05/26 00:00 [received] PHST- 2015/09/29 00:00 [revised] PHST- 2015/10/09 00:00 [accepted] PHST- 2015/10/17 06:00 [entrez] PHST- 2015/10/17 06:00 [pubmed] PHST- 2016/05/11 06:00 [medline] PHST- 2018/06/25 00:00 [pmc-release] AID - 10.1002/hep.28285 [doi] PST - ppublish SO - Hepatology. 2016 Jan;63(1):233-46. doi: 10.1002/hep.28285. Epub 2015 Nov 23.