title: Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease.
abstract: It is unclear whether TGF-beta, a critical differentiation factor for T cells producing interleukin 17 (T(H)-17 cells), is required for the initiation of experimental autoimmune encephalomyelitis (EAE) in vivo. Here we show that mice whose T cells cannot respond to TGF-beta signaling lack T(H)-17 cells and do not develop EAE despite the presence of T helper cell type 1 infiltrates in the spinal cord. Local but not systemic antibody blockade of TGF-beta prevented T(H)-17 cell differentiation and the onset of EAE. The pathogen stimulus zymosan, like mycobacterium, induced T(H)-17 cells and initiated EAE, but the disease was transient and correlated with reduced production of interleukin 23. These data show that TGF-beta is essential for the initiation of EAE and suggest that disease progression may require ongoing chronic inflammation and production of interleukin 23.
authors.affiliation: Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Veldhoen
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hocking
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007106:Immune Sera / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*
chemical_list: D007106:Immune Sera; D053759:Interleukin-23; D016212:Transforming Growth Factor beta