title: Co-stimulation of TLR4 and Dectin-1 Induces the Production of Inflammatory Cytokines but not TGF-β for Th17 Cell Differentiation.
abstract: Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-β. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct CD4(+) T cells to Th17 cells. Addition of TGF-β but not IL-6 or IL-1β was able to promote IL-17 production from CD4(+) T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-β production is a limiting factor for promoting Th17 immunity.
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Chang
authors.affiliation: Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
keywords: Dectin-1; IL-17; TGF-β; TLR