New roles for CD14 and IL-beta linking inflammatory dendritic cells to IL-17 production in memory CD4(+) T cells

Juan M. Ilarregui, Astrid J. van Beelen, Cynthia M. Fehres, Sven C. M. Bruijns, Juan J. Garcia-Vallejo, Yvette van Kooyk

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18 Citations (Scopus)


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
Original languageEnglish
Pages (from-to)907-916
JournalImmunology and Cell Biology
Issue number10
Publication statusPublished - 2016

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