Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization.
Neuropeptide Y (NPY), a major autonomic nervous system and stress mediator, is emerging as an important regulator of inflammation, implicated in autoimmunity, asthma, atherosclerosis, and cancer. Yet the role of NPY in regulating phenotype and functions of dendritic cells (DCs), the professional antigen-presenting cells, remains undefined. Here we investigated whether NPY could induce DCs to migrate, mature, and polarize naive T lymphocytes. We found that NPY induced a dose-dependent migration of human monocyte-derived immature DCs through the engagement of NPY Y1 receptor and the activation of ERK and p38 mitogen-activated protein kinases. NPY promoted DC adhesion to endothelial cells and transendothelial migration. It failed to induce phenotypic DC maturation, whereas it conferred a T helper 2 (Th2) polarizing profile to DCs through the up-regulation of interleukin (IL)-6 and IL-10 production. Thus, during an immune/inflammatory response NPY may exert proinflammatory effects through the recruitment of immature DCs, but it may exert antiinflammatory effects by promoting a Th2 polarization. Locally, at inflammatory sites, cell recruitment could be amplified in conditions of intense acute, chronic, or cold stress. Thus, altered or amplified signaling through the NPY-NPY-Y1 receptor-DC axis may have implications for the development of inflammatory conditions.-Buttari, B., Profumo, E., Domenici, G., Tagliani, A., Ippoliti, F., Bonini, S., Businaro, R., Elenkov, I., Riganò, R. Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization.
Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy;
Brigitta
B
Buttari
Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy;
Elisabetta
E
Profumo
Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy;
Giacomo
G
Domenici
Department of Medico-Surgical Sciences and Biotechnologies and.
Angela
A
Tagliani
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; and.
Flora
F
Ippoliti
Institute of Neurobiology and Molecular Medicine, Italian National Research Council, Rome, Italy.
Sergio
S
Bonini
Department of Medico-Surgical Sciences and Biotechnologies and.
Rita
R
Businaro
Institute of Neurobiology and Molecular Medicine, Italian National Research Council, Rome, Italy.
Ilia
I
Elenkov
Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; rachele.rigano@iss.it.
Rachele
R
Riganò
D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y; D018418:Th2 Cells / Q000378:metabolism / Q000502:physiology*; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015850:Interleukin-6; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases
DC maturation; MAPKs; adhesion to endothelial cells; cytokines; neuromediators; transendothelial migration