Interferon-alpha and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets

Toll 样受体 7 配体在人类血液树突状细胞亚群中以不同的方式诱导干扰素 α 和白细胞介素 12

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作者:Tomoki Ito, Ryuichi Amakawa, Tsuneyasu Kaisho, Hiroaki Hemmi, Kenichirou Tajima, Kazutaka Uehira, Yoshio Ozaki, Hideyuki Tomizawa, Shizuo Akira, Shirou Fukuhara

Abstract

Dendritic cells (DCs) play a crucial role in the immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). In humans, two distinct DC subsets, CD11c(-) plasmacytoid DCs (PDCs) and CD11c(+) myeloid DCs (MDCs), have been identified and can respond to different TLR ligands, depending on the differential expression of cognate TLRs. In this study, we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival of the subsets and upregulated the surface expression of costimulatory molecules such as CD40, CD80, and CD86. However, the cytokine induction pattern was distinct in that PDCs and MDCs produced interferon (IFN)-alpha and interleukin (IL)-12, respectively. In response to TLR-7 ligands, the Th1 cell supporting ability of both DC subsets was enhanced, depending on the cytokines the respective subsets produced. This study demonstrates that TLR-7 exerts its biological effect in a DC subset-specific manner.

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