title: Tolerogenic IDO(+) Dendritic Cells Are Induced by PD-1-Expressing Mast Cells.
abstract: Mast cells (MCs) are tissue resident cells, rich in inflammatory mediators, involved in allergic reactions, and with an increasingly recognized role in immunomodulation. Dendritic cells (DCs), on the other hand, are central to the determination of immune response patterns, being highly efficient antigen-presenting cells that respond promptly to changes in their microenvironment. Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact with MC (MC-iDC) decreased HLA-DR but increased PD-L1 expression and stimulated regulatory T lymphocytes, which expresses FoxP3(+), secrete TGF-β and IL-10, and suppress the proliferation of mitogen-stimulated naïve T lymphocytes. Furthermore, MC-iDC expressed higher levels of indoleamine-2,3-deoxigenase (IDO), a phenomenon that was blocked by treatment of MC with anti-PD-1 or by the treatment of DCs with anti-PD-L1 or anti-PD-L2, but not by blocking of H1 and H2 histamine receptors on DCs. Contact with MC also increased phosphorylated STAT-3 levels in iDCs. When a STAT-3 inhibitor, JSI-124, was added to the DCs before contact with MC, the MC-iDC recovered their ability to induce allogeneic T cell proliferation and did not increase their IDO expression.
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , São Paulo , Brazil.
authors.forename: Cecilia Pessoa
authors.initials: CP
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , São Paulo , Brazil.
authors.forename: Ana Carolina Franco
authors.initials: AC
authors.lastname: Ferreira
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , São Paulo , Brazil.
authors.forename: Mariana Pereira
authors.initials: MP
authors.lastname: Pinho
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , São Paulo , Brazil.
authors.forename: Cristiano Jacob
authors.initials: CJ
authors.lastname: de Moraes
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , São Paulo , Brazil.
authors.forename: Patrícia Cruz
authors.initials: PC
authors.lastname: Bergami-Santos
authors.affiliation: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil; Center for Cellular and Molecular Studies and Therapy (NETCEM), University of Sao Paulo, São Paulo, Brazil.
authors.forename: José Alexandre Marzagão
authors.initials: JA
authors.lastname: Barbuto
keywords: IDO; STAT-3; Tregs; mast cells; tolerogenic DCs
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