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Hong Nian; Ligation of Toll-like receptor 7 (TLR7) by CL097 enhances the IL-17+ uveitogenic T cell responses via p38 signaling in Dendritic cells (DCs). Invest. Ophthalmol. Vis. Sci. 2014;55(13):96.
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To characterize the role and mechanism of TLR7 on the activation of IL-17+ uveitogenic T cells
C57BL/6 (B6) mice were immunized with the uveitogenic peptide IRBP1-20 in complete (CFA) Freund’s adjuvant. In vivo-primed T cells were stimulated with the immunizing peptide and bone marrow derived Dendritic cells (DCs) in the absence or presence of CL097. DCs were examined for expression and production of IL-1β, IL-6 and IL-23. Activated T cells were analyzed for expression and production of IL-17.
After CL097 treatment, DCs exhibited upregulation of MHC class II and CD86. CL097 treated DCs (CL097-DC) upregulated the mRNA and protein expression of IL-1β, IL-6 and IL-23 , and they gained increased ability of promoting IL-17+ T cell responses. CL097 treatment activated p38 mitogen-activated protein kinase (p38 MAPK) in DC. Inhibition of p38 MAPK signaling suppressed CL097-DC expression of IL-1β, IL-6 and IL-23 and blocked CL097-DC stimulation of Th17 responses.
Treatment by CL097 enhances the IL-17+ uveitogenic T cell responses. This effect may be mediated, at least in part, by the activation of p38 signaling pathway in DCs.
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