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

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.

journal_name

Blood

journal_title

Blood

authors

Gregori S,Tomasoni D,Pacciani V,Scirpoli M,Battaglia M,Magnani CF,Hauben E,Roncarolo MG

doi

10.1182/blood-2009-07-234872

subject

Has Abstract

pub_date

2010-08-12 00:00:00

pages

935-44

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2009-07-234872

journal_volume

116

pub_type

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