title: GM-CSF plays a key role in zymosan-stimulated human dendritic cells for activation of Th1 and Th17 cells.
abstract: In this study, we compared the effects of zymosan and LPS on human monocyte-derived dendritic cells. The specific effects of zymosan on the expression of several key cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukins (IL-1α, IL-1β and IL-12 p70) were quite distinct from the effects of LPS. Unlike activation with LPS, DCs activated by zymosan expressed little or no IL-12 p70 due to lack of expression of the p35 subunit. However, treatment with zymosan resulted in a substantial increase in Th1 and Th17 cell-polarizing capacity of DCs. Furthermore, the GM-CSF secreted by zymosan-activated DCs enhanced IL-23 production, resulting in activation of a Th17 response. GM-CSF and IL-27, rather than IL-12 p70, were both major direct contributors to the activation of a Th1 response. This signaling mechanism is distinct and yet complementary to LPS-mediated T-cell activation. We suggest that this novel zymosan-induced GM-CSF-mediated signaling network may play a key role in regulating specific immune cell type activities.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taiwan, ROC.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Wei
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Su
authors.forename: Swey-Shen
authors.initials: SS
authors.lastname: Chen
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.forename: Ning-Sun
authors.initials: NS
authors.lastname: Yang
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015054:Zymosan