title: CCL18 differentiates dendritic cells in tolerogenic cells able to prime regulatory T cells in healthy subjects.
abstract: The aim of this study was to evaluate the nonchemotactic function of CCL18 on human dendritic cells (DCs). In different protocols of DC differentiation, CCL18 was highly produced, suggesting that it may constitute a mandatory mediator of the differentiation process. Differentiation of monocytes from healthy subjects in the presence of granulocyte-macrophage colony-stimulating factor and CCL18 led to the development of DCs with a semimature phenotype, with intermediate levels of costimulatory and MHC class II molecules, increased CCR7 expression, which induced, in coculture with allogenic naive T cells, an increase in IL-10 production. The generated T cells were able to suppress the proliferation of effector CD4(+)CD25(-) cells, through a cytokine-dependent mechanism, and exhibited characteristics of type 1 T regulatory cells. The generation of tolerogenic DCs by CCL18 was dependent on the production of indoleamine 2,3-dioxigenase through an interleukin-10-mediated mechanism. Surprisingly, when DCs originated from allergic patients, the tolerogenic effect of CCL18 was lost in relation with a decreased binding of CCL18 to its putative receptor. This study is the first to define a chemokine able to generate tolerogenic DCs. However, this function was absent in allergic donors and may participate to the decreased tolerance observed in allergic diseases.
authors.affiliation: Pulmonary Immunity, Inserm U1019, Lille, France.
authors.forename: Imane
authors.initials: I
authors.lastname: Azzaoui
authors.forename: Saliha Ait
authors.initials: SA
authors.lastname: Yahia
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Han
authors.initials: H
authors.lastname: Vorng
authors.forename: Olivier
authors.initials: O
authors.lastname: Morales
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Nadira
authors.initials: N
authors.lastname: Delhem
authors.forename: Coline
authors.initials: C
authors.lastname: Ple
authors.forename: André-Bernard
authors.initials: AB
authors.lastname: Tonnel
authors.forename: Benoit
authors.initials: B
authors.lastname: Wallaert
authors.forename: Anne
authors.initials: A
authors.lastname: Tsicopoulos
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006262:Health; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D061251:Primary Cell Culture; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D016753:Interleukin-10