Atrial natriuretic peptide is a cardiovascular hormone secreted mainly by the cardiac atria and regulates the volume-pressure homeostasis. The action of ANP is mediated by GC-A.We previously reported that human monocyte-derived dendritic cells express GC-A and respond to ANP with polarization toward a Th2-inducing phenotype. In the present study, we explored the possibility that pDC are subjected to immunoregulation via the ANP/GC-A system.We examined GC-A expression on blood pDC and found that GC-A was not expressed on fresh pDC but was induced after stimulation with CpG-oligodeoxynucleotide AAC-30, IL-3, or interleukin-3 plus CD40 ligand. Activated pDC responded to ANP with an increase in cGMP production, indicating that GC-A expressed on pDC was functional. We investigated whether tonsillar pDC express GC-A by immunohistochemistry and immunofluorescence staining. We found that GC-A+ HLA-DR+ cells were present in the T-cell areas and the perivascular areas. Flow cytometric analysis with tonsillar cells confirmed that lineage- CD123high pDC express GC-A. These results indicate that the ANP/GC-A system is involved in immune regulation through pDC in secondary lymphoid organs.
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