PMID- 26834749 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160202 LR - 20190109 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 7 DP - 2016 TI - Tolerogenic IDO(+) Dendritic Cells Are Induced by PD-1-Expressing Mast Cells. PG - 9 LID - 10.3389/fimmu.2016.00009 [doi] LID - 9 AB - 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-beta and IL-10, and suppress the proliferation of mitogen-stimulated naive 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. FAU - Rodrigues, Cecilia Pessoa AU - Rodrigues CP AD - Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil. FAU - Ferreira, Ana Carolina Franco AU - Ferreira AC AD - Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil. FAU - Pinho, Mariana Pereira AU - Pinho MP AD - Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil. FAU - de Moraes, Cristiano Jacob AU - de Moraes CJ AD - Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil. FAU - Bergami-Santos, Patricia Cruz AU - Bergami-Santos PC AD - Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil. FAU - Barbuto, Jose Alexandre Marzagao AU - Barbuto JA AD - Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Center for Cellular and Molecular Studies and Therapy (NETCEM), University of Sao Paulo, Sao Paulo, Brazil. LA - eng PT - Journal Article DEP - 20160125 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC4724729 OTO - NOTNLM OT - IDO OT - STAT-3 OT - Tregs OT - mast cells OT - tolerogenic DCs EDAT- 2016/02/03 06:00 MHDA- 2016/02/03 06:01 PMCR- 2016/01/01 CRDT- 2016/02/03 06:00 PHST- 2015/11/10 00:00 [received] PHST- 2016/01/11 00:00 [accepted] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/02/03 06:01 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2016.00009 [doi] PST - epublish SO - Front Immunol. 2016 Jan 25;7:9. doi: 10.3389/fimmu.2016.00009. eCollection 2016.