title: Neurodegeneration Enhances the Development of Arthritis.
abstract: The prevalence of neurodegenerative disease and arthritis increases with age. Despite both processes being associated with immune activation and inflammation, little is known about the mechanistic interactions between neurodegenerative disease and arthritis. In this article, we show that tau-transgenic (tau-tg) mice that develop neurodegenerative disease characterized by deposition of tau tangles in the brain are highly susceptible to developing arthritis. Already at steady-state conditions, tau-tg mice exhibit peripheral immune activation that is manifested by higher numbers of granulocytes, plasmablasts, and inflammatory Ly6ChiCCR2+monocytes, as well as increased levels of proinflammatory cytokines, such as TNF-α and IL-17. Upon induction of collagen-induced arthritis (CIA), tau-tg mice displayed an increased incidence and an earlier onset of CIA that was associated with a more pronounced inflammatory cytokine response. Furthermore, induction of CIA led to significantly elevated numbers of Iba-1-expressing cells in the brain, indicative of microglia activation, and the formation of anti-tau Abs in tau-tg mice. These changes were accompanied by the resolution of tau tangles and significantly decreased neurodegenerative pathology. In summary, these data show that neurodegenerative disease enhances the development of arthritis. In addition, arthritis, once induced, triggers innate immune responses in the brain, leading to resolution of neurodegenerative changes.
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Lang
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Ulrike
authors.identifier: 0000-0003-2934-3202
authors.initials: U
authors.lastname: Harre
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine 3, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Pavitra
authors.initials: P
authors.lastname: Purohit
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Katharina
authors.identifier: 0000-0001-6866-0388
authors.initials: K
authors.lastname: Dietel
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Deborah
authors.identifier: 0000-0003-0966-3639
authors.initials: D
authors.lastname: Kienhöfer
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Wolfgang
authors.identifier: 0000-0002-2518-5094
authors.initials: W
authors.lastname: Baum
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and.
authors.forename: Martin
authors.identifier: 0000-0002-0258-2484
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and georg.schett@uk-erlangen.de dirk.mielenz@fau.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; and georg.schett@uk-erlangen.de dirk.mielenz@fau.de.|Division of Molecular Immunology, Department of Internal Medicine 3, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mielenz
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D001323:Autoantibodies / Q000097:blood; D001921:Brain / Q000276:immunology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000276:immunology*; D019636:Neurodegenerative Diseases; D016874:Neurofibrillary Tangles / Q000276:immunology; D016875:tau Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C491049:Aif1 protein, mouse; D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D016207:Cytokines; C558298:Mapt protein, mouse; D008840:Microfilament Proteins; D016875:tau Proteins