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|Title:||Differentiation of type 1 T regulatory (Tr1) cells by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway|
|Citation:||Blood, 2010; 116(6):935-944|
|Publisher:||Amer Soc Hematology|
|Silvia Gregori, Daniela Tomasoni, Valentina Pacciani, Miriam Scirpoli, Manuela Battaglia, Chiara Francesca Magnani, Ehud Hauben, and Maria-Grazia Roncarolo|
|Abstract:||Type 1 T regulatory (Tr1) cells suppress immune responses in vivo and in vitro and play a key role in maintaining tolerance to self- and non–self-antigens. Interleukin-10 (IL-10) is the crucial driving factor for Tr1 cell differentiation, but the molecular mechanisms underlying this induction remain unknown. We identified and characterized a subset of IL-10–producing human dendritic cells (DCs), termed DC-10, which are present in vivo and can be induced in vitro in the presence of IL-10. DC-10 are CD14+, CD16+, CD11c+, CD11b+, HLA-DR+, CD83+, CD1a−, CD1c−, express the Ig-like transcripts (ILTs) ILT2, ILT3, ILT4, and HLA-G antigen, display high levels of CD40 and CD86, and up-regulate CD80 after differentiation in vitro. DC-10 isolated from peripheral blood or generated in vitro are potent inducers of antigen-specific IL-10–producing Tr1 cells. Induction of Tr1 cells by DC-10 is IL-10–dependent and requires the ILT4/HLA-G signaling pathway. Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.|
|Keywords:||Dendritic Cells; Monocytes; Humans; Membrane Glycoproteins; Receptors, Immunologic; Interleukin-10; Interleukin-12; Histocompatibility Antigens Class I; HLA Antigens; Flow Cytometry; Immunophenotyping; Cell Communication; Signal Transduction; Cell Differentiation; Immune Tolerance; Gene Expression; T-Lymphocytes, Regulatory; HLA-G Antigens|
|Rights:||© 2010 by The American Society of Hematology|
|Appears in Collections:||Surgery publications|
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