title: The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells.
abstract: Mechanisms linking innate immunity and autoimmune responses are poorly understood. Myeloid-related protein-8 (Mrp8) and Mrp14 are damage-associated molecular pattern molecules (DAMPs) highly upregulated in various autoimmune disorders. We show in a mouse autoimmune model that local Mrp8 and Mrp14 production is essential for the induction of autoreactive CD8+ T cells and the development of systemic autoimmunity. This effect is mediated via Toll-like receptor 4 (TLR4) signaling leading to increased interleukin-17 (IL-17) expression. Notably, expression of Mrp8 and Mrp14 was upregulated in cutaneous lupus erythematosus, and stimulation of CD8+ T cells from individuals with lupus erythematosus with MRP proteins resulted in an upregulation of IL-17, suggesting a key role for MRP8 and MRP14 for the development of autoreactive lymphocytes during human autoimmunity as well. These results demonstrate a link between local expression of DAMP molecules and the development of systemic autoimmunity.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany. loserk@uni-muenster.de
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.forename: Maik
authors.initials: M
authors.lastname: Voskort
authors.forename: Aloys
authors.initials: A
authors.lastname: Lueken
authors.forename: Verena
authors.initials: V
authors.lastname: Kupas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nacken
authors.forename: Lars
authors.initials: L
authors.lastname: Klenner
authors.forename: Annegret
authors.initials: A
authors.lastname: Kuhn
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Stefan
authors.initials: S
authors.lastname: Beissert
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000276:immunology* / Q000502:physiology; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D040501:Calgranulin A / Q000276:immunology* / Q000502:physiology; D040502:Calgranulin B / Q000276:immunology* / Q000502:physiology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology / Q000502:physiology
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D020381:Interleukin-17; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D023201:CD40 Ligand
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