Increase of Alternatively Activated Antigen Presenting Cells in Active Experimental Autoimmune Encephalomyelitis
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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.
KeywordsMultiple sclerosis Next generation sequencing Dendritic cell Microglia Autoimmunity CNS infiltration
We thank Birgit Hohmann, Christin Liefländer, Andreas Zymny, Kristian Schütze, and Heike Ehrengard for technical assistance and Darragh O’Neill for proofreading the manuscript.
B.W. performed all experiments, analyzed data, drafted the manuscript, and prepared Figs. G.P. performed experiments. M.H. analyzed RNA-Seq data. M.K. performed RNA-Seq experiments. F.L. and K.D. interpreted results. T.B. performed cell sort experiments. F.Z. designed the study, interpreted results and edited manuscript. E.W. designed the study, conceptually designed figures, interpreted results and wrote the manuscript.
Compliance with Ethical Standards
Sources of Support
This study has been supported by the German Research Foundation (DFG, SFB-TR 128/B4 to F.Z. and T.B. and DFG, SFB-TR 128/A5 to K.D.).
Conflict of Interest
The authors declare that they have no conflict of interest.
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