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

作者：Ilarregui Juan M^*; van Beelen Astrid J; Fehres Cynthia M; Bruijns Sven C M; Garcia Vallejo Juan J; van Kooyk Yvette

来源：Immunology and Cell Biology, 2016, 94(10): 907-916.

DOI：10.1038/icb.2016.66

Interleukin (IL)-1 beta has proven to be crucial in the differentiation of human and mouse Th17 cells. Although it has become evident that IL-1 beta has potent IL-17-inducing effects on CD4(+) T cells directly, it has not yet been explored whether IL-1 beta can also prime dendritic cells (DCs) for a Th17 instruction program. Here, we show that human immature DCs exposed to IL-1 beta promote IL-17 production in human memory CD4(+) T cells. IL-1 beta-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-gamma 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-1 beta 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-1 beta 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.

• 出版日期2016-12