title: TLR7 Engagement on Dendritic Cells Enhances Autoreactive Th17 Responses via Activation of ERK.
abstract: In this study, we showed that TLR7 activation significantly promoted interphotoreceptor retinoid-binding protein (IRBP)-specific Th17 responses by upregulating RORγt, IL-17, GM-CSF, and IL-23R expression in experimental autoimmune uveitis mice. In vivo administration of CL097 activated dendritic cells (DCs) and endowed them with an increased ability to activate IRBP-specific Th17 cells. CL097-treated DCs (CL097-DCs) formed a cytokine milieu that favored the generation and maintenance of Th17 cells by stimulating IL-1β, IL-6, and IL-23 expression. Furthermore, IRBP-specific T cells from immunized mice injected with CL097-DCs produced more IL-17 and transferred more severe experimental autoimmune uveitis than did those from mice injected with DCs. The enhanced immunostimulatory activities of CL097-DCs depended on JNK, ERK, and p38 activation. Blockade of ERK, but not p38 or JNK, completely abolished the Th17 responses induced by CL097-DCs. Collectively, our findings suggest that CL097 treatment significantly promotes autoreactive IL-17+T cell responses through enhancing DC activation, which is mediated, at least in part, via the activation of ERK signaling.
authors: Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry and Ophthalmology, Tianjin 300384, China.
authors: Qing
authors: Q
authors: Xiao
authors: Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry and Ophthalmology, Tianjin 300384, China.
authors: Xue
authors: X
authors: Li
authors: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90033; and.
authors: Deming
authors: 0000-0003-4851-0416
authors: D
authors: Sun
authors: The First Hospital and Institute of Immunology, Jilin University, Changchun 130061, China.
authors: Huanfa
authors: H
authors: Yi
authors: Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry and Ophthalmology, Tianjin 300384, China.
authors: Xiaoxiao
authors: X
authors: Lu
authors: Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry and Ophthalmology, Tianjin 300384, China; nianhong@126.com.
authors: Hong
authors: 0000-0002-9983-3410
authors: H
authors: Nian
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D007093:Imidazoles / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics; D015850:Interleukin-6 / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D011804:Quinolines / Q000494:pharmacology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000276:immunology; D015398:Signal Transduction; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology* / Q000378:metabolism*; D014605:Uveitis / Q000276:immunology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D007093:Imidazoles; D020381:Interleukin-17; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011804:Quinolines; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D012177:Retinol-Binding Proteins; D051199:Toll-Like Receptor 7; D000099214:Retinol-Binding Proteins, Interstitial; C547051:CL097 compound; C572370:Csf2ra protein, mouse; C477038:Tlr7 protein, mouse; C528688:interleukin-23 receptor, mouse; C577686:interleukin-6, mouse