Atrial natriuretic peptide polarizes human dendritic cells toward a Th2-promoting phenotype through its receptor guanylyl cyclase-coupled receptor A.
Atrial natriuretic peptide (ANP) is a cardiovascular hormone secreted mainly by the cardiac atria and regulates the volume-pressure homeostasis. The action of ANP is mediated by its receptor, guanylyl cyclase-coupled receptor A (GC-A). In this study, we explored the possibility that ANP and GC-A may play a role in the dendritic cell (DC)-mediated immune regulation. We first examined the expression of GC-A in human monocyte-derived DCs in comparison with monocytes and found that DCs but not monocytes express GC-A at both the mRNA and protein levels. DCs responded to ANP with an increase in intracellular cGMP in a dose-dependent manner, indicating that GC-A expressed on DCs is functional. Furthermore, treatment of DCs with ANP decreased production of IL-12 and TNF-alpha and conversely increased that of IL-10 upon stimulation with LPS. In accordance with this change of cytokine production, DCs treated with ANP plus LPS promoted differentiation of naive CD4(+) T cells into a Th2 phenotype. Finally, we presented evidence that ANP affected cytokine production of fresh whole blood stimulated with LPS in line with the above-mentioned results. These results indicate that ANP polarizes human DCs toward a Th2-promoting phenotype through GC-A and thus can regulate immune responses.
Morita
Rimpei
R
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ukyo
Naoya
N
Furuya
Mayumi
M
Uchiyama
Takashi
T
Hori
Toshiyuki
T
D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D006162:Guanylate Cyclase / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology; D007519:Isoantigens / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000201:enzymology; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis / Q000502:physiology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D007519:Isoantigens; D008070:Lipopolysaccharides; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A