title: Cutting edge: IL-6-dependent autoimmune disease: dendritic cells as a sufficient, but transient, source.
abstract: Mice lacking IL-6 are resistant to autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), which is driven by CNS-reactive CD4(+) T cells. There are multiple cellular sources of IL-6, but the critical source in EAE has been uncertain. Using cell-specific IL-6 deficiency in models of EAE induced by active immunization, passive transfer, T cell transfer, and dendritic cell transfer, we show that neither the pathogenic T cells nor CNS-resident cells are required to produce IL-6. Instead, the requirement for IL-6 was restricted to the early stages of T cell activation and was entirely controlled by dendritic cell-derived IL-6. This reflected the loss of IL-6R expression by T cells over time. These data explain why blockade of IL-6R only achieves protection against EAE if used at the time of T cell priming. The implications for therapeutic manipulation of IL-6 signaling in human T cell-driven autoimmune conditions are considered.
authors.affiliation: Medical Research Council Centre for Inflammation Research, Centre for Multiple Sclerosis Research and Centre for Immunity, Infection, and Evolution, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Leech
authors.forename: Tom A
authors.initials: TA
authors.lastname: Barr
authors.forename: Darryl G
authors.initials: DG
authors.lastname: Turner
authors.forename: Sheila
authors.initials: S
authors.lastname: Brown
authors.forename: Richard A
authors.initials: RA
authors.lastname: O'Connor
authors.forename: David
authors.initials: D
authors.lastname: Gray
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Mellanby
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Anderton
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007116:Immunization, Passive; D015850:Interleukin-6 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D037182:T-Cell Antigen Receptor Specificity
chemical_list: D001324:Autoantigens; C489629:H-2A(b) antigen, mouse; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D008222:Lymphokines; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019947:Receptors, Interleukin-6; C577686:interleukin-6, mouse; C074815:myelin basic protein 1-9; C445081:myelin oligodendrocyte glycoprotein (35-55)