title: Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain.
abstract: Brain-intrinsic degenerative cascades have been proposed to be an initial factor driving lesion formation in multiple sclerosis (MS). Here, we identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the mouse forebrain. Female C57BL/6 mice were fed cuprizone for 3 weeks, followed by a period of 2 weeks on normal chow to induce the formation of lesion foci in the forebrain. Subsequent immunization with myelin oligodendrocyte glycoprotein 35-55 peptide, which induces myelin autoreactive T cells in the periphery, resulted in massive immune cell recruitment into the affected forebrain. Additional adoptive transfer experiments together with flow cytometry analysis underline the importance of brain-derived signals for immune cell recruitment. This study clearly illustrates the significance of brain-intrinsic degenerative cascades for immune cell recruitment and MS lesion formation. Additional studies have to address the signaling cascades and mechanistic processes that form the top-down communication between the affected brain area, neurovascular unit, and peripheral immune cells.
  
  
  CONCLUSIONS
  We identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the forebrain. Thus, immune cell recruitment might be a second step during the formation of new inflammatory lesions in multiple sclerosis. A better understanding of factors regulating neurodegeneration-induced immune cell recruitment will pave the way for the development of novel therapeutic treatment strategies.
authors.affiliation: Institute of Neuroanatomy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Scheld
authors.affiliation: Institute of Neuroanatomy.
authors.forename: Bernhard Josef
authors.initials: BJ
authors.lastname: Rüther
authors.affiliation: Institute of Neuroanatomy.
authors.forename: René
authors.initials: R
authors.lastname: Große-Veldmann
authors.affiliation: Department of Pediatrics, and.
authors.forename: Kim
authors.initials: K
authors.lastname: Ohl
authors.affiliation: Department of Pediatrics, and.
authors.forename: Klaus
authors.initials: K
authors.lastname: Tenbrock
authors.affiliation: Institute of Pharmacology and Toxicology, Faculty of Medicine, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dreymüller
authors.affiliation: Institute of Pathology and Neuropathology, University of Tuebingen, D-72076 Tuebingen, Germany, and.
authors.forename: Petra
authors.initials: P
authors.lastname: Fallier-Becker
authors.affiliation: Institute of Neuroanatomy.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Institute of Neuroanatomy.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Institute of Neuroanatomy.
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
authors.affiliation: Department of Anatomy II, Ludwig Maximilians University of Munich, D-80336 Munich, Germany markus.kipp@med.uni-muenchen.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002614:Chelating Agents / Q000633:toxicity; D003471:Cuprizone / Q000633:toxicity; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology; D037342:Pertussis Toxin / Q000633:toxicity; D016548:Prosencephalon / Q000473:pathology*
chemical_list: C491049:Aif1 protein, mouse; D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D002614:Chelating Agents; D008840:Microfilament Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D003471:Cuprizone; D005620:Freund's Adjuvant; D037342:Pertussis Toxin
keywords: cytodegeneration; invasion; trigger
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