title: Increase of Alternatively Activated Antigen Presenting Cells in Active Experimental Autoimmune Encephalomyelitis.
abstract: The importance of CD11c+antigen-presenting cells (APCs) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) is well accepted and the gate keeper function of perivascular CD11c+APCs has been demonstrated. CD11c can be expressed by APCs from external sources or by central nervous system (CNS) resident APCs such as microglia. Yet, changes in the gene expression pattern of CNS CD11c+APCs during disease are still unclear and differentially expressed genes might play a decisive role in EAE progression. Due to their low numbers in the diseased brain and due to the absence of considerable numbers in the healthy CNS, analysis of CNS CD11c+cells is technically difficult. To ask whether the CD11c+APC population contributes to remission of EAE disease, we used Illumina deep mRNA sequencing (RNA-Seq) and quantitative real time polymerase chain reaction (qRT-PCR) analyses to identify the transcriptome of CD11c+APCs during disease course. We identified a battery of genes that were significantly regulated during the exacerbation of the disease compared to remission and relapse. Three of these genes, Arginase-1, Chi3l3 and Ms4a8a, showed a higher expression at the exacerbation than at later time points during the disease, both in SJL/J and in C57BL/6 mice, and could be attributed to alternatively activated APCs. Expression of Arginase-1, Chi3l3 and Ms4a8a genes was linked to the disease phase of EAE rather than to disease score. Expression of these genes suggested that APCs resembling alternatively activated macrophages are involved during the first wave of neuroinflammation and can be directly associated with the disease progress.
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Wasser
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.|Focus Program Translational Neuroscience (FTN) & Institute for Microscopic Anatomy and Neurobiology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Gautam
authors.initials: G
authors.lastname: Pramanik
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Hess
authors.affiliation: Institute for Immunology, Research Center Immunology (FZI), University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Luessi
authors.affiliation: Institute of Clinical Neuroimmunology, University Hospital Grosshadern, LMU Munich, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.affiliation: Institute for Immunology, Research Center Immunology (FZI), University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.|Focus Program Translational Neuroscience (FTN) & Institute for Microscopic Anatomy and Neurobiology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany. esther.witsch@gmail.com.|Focus Program Translational Neuroscience (FTN) & Institute for Microscopic Anatomy and Neurobiology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany. esther.witsch@gmail.com.
authors.forename: Esther
authors.initials: E
authors.lastname: Witsch
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D039521:CD11c Antigen / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053263:Gene Regulatory Networks / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D039521:CD11c Antigen
keywords: Autoimmunity; CNS infiltration; Dendritic cell; Microglia; Multiple sclerosis; Next generation sequencing