title: New roles for CD14 and IL-β linking inflammatory dendritic cells to IL-17 production in memory CD4+T cells.
abstract: Interleukin (IL)-1β has proven to be crucial in the differentiation of human and mouse Th17 cells. Although it has become evident that IL-1β has potent IL-17-inducing effects on CD4+T cells directly, it has not yet been explored whether IL-1β can also prime dendritic cells (DCs) for a Th17 instruction program. Here, we show that human immature DCs exposed to IL-1β promote IL-17 production in human memory CD4+T cells. IL-1β-primed DCs express high levels of CD14 that mediate IL-17 production through direct interaction with T cells. Moreover, culturing human CD4+CD45RO+memory T cells with soluble CD14 is sufficient for the upregulation of retinoic acid-related orphan receptor-γ thymus and IL-17 production. In addition, in a human in situ model using tissue-resident skin DCs, upregulation of CD14 expression induced by IL-1β on skin residents DCs promotes IL-17 production in memory T cells; strongly suggesting the in vivo relevance of this mechanism. Our findings uncover new roles for IL-1β and CD14, and may therefore have important consequences for the development of new therapies for Th17-mediated autoimmune diseases and bacterial and fungal pathogenic infections.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Ilarregui
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Astrid J
authors.initials: AJ
authors.lastname: van Beelen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Fehres
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sven C M
authors.initials: SC
authors.lastname: Bruijns
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: García-Vallejo
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D010641:Phenotype; D012867:Skin / Q000473:pathology; D012995:Solubility; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010457:Peptidoglycan