The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting.
Much remains to be learned about the physiologic events that promote monocytes to become lymph-homing dendritic cells (DCs). In a model of transendothelial trafficking, some monocytes become DCs in response to endogenous signals. These DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse transmigration), reminiscent of the migration into lymphatic vessels. Here we show that the subpopulation of monocytes that expresses CD16 (Fcgamma receptor III) is predisposed to become migratory DCs. The vast majority of cells derived from CD16(+) monocytes reverse transmigrated, and their presence was associated with migratory cells expressing high levels of CD86 and human histocompatibility leukocyte antigen (HLA)-DR, and robust capacity to induce allogeneic T cell proliferation. A minority of CD16(-) monocytes reverse transmigrated, and these cells stimulated T cell proliferation less efficiently. CD16 was not functionally required for reverse transmigration, but promoted cell survival when yeast particles (zymosan) were present as a maturation stimulus in the subendothelial matrix. The cell surface phenotype and migratory characteristics of CD16(+) monocytes were inducible in CD16(-) monocytes by preincubation with TGFbeta1. We propose that CD16(+) monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels.
The Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA. gwendalyn.randolph@mssm.edu
Gwendalyn J
GJ
Randolph
Guzman
G
Sanchez-Schmitz
Ronald M
RM
Liebman
Knut
K
Schäkel
D000938:Antigen-Presenting Cells / Q000276:immunology; D015415:Biomarkers; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D015054:Zymosan / Q000494:pharmacology
D015415:Biomarkers; D006684:HLA-DR Antigens; D017452:Receptors, IgG; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015054:Zymosan