Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway

Silvia Gregori, Daniela Tomasoni, Valentina Pacciani, Miriam Scirpoli, Manuela Battaglia, Chiara Francesca Magnani, Ehud Hauben, Maria Grazia Roncarolo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)935-944
Number of pages10
JournalBlood
Volume116
Issue number6
DOIs
Publication statusPublished - Aug 12 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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