title: Differential regulation of human blood dendritic cell subsets by IFNs.
abstract: Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10-producing regulatory T cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3-primed CD11c(-) DCs activated T cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan. amakawa@takii.kmu.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: R
authors.initials: R
authors.lastname: Amakawa
authors.forename: M
authors.initials: M
authors.lastname: Inaba
authors.forename: S
authors.initials: S
authors.lastname: Ikehara
authors.forename: K
authors.initials: K
authors.lastname: Inaba
authors.forename: S
authors.initials: S
authors.lastname: Fukuhara
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007372:Interferons / Q000097:blood / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018121:Receptors, Cytokine / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D007372:Interferons