title: Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE.
abstract: EAE, an animal model for MS, is a Th17 and Th1-cell-mediated autoimmune disease, but the mechanisms leading to priming of encephalitogenic T cells in autoimmune neuroinflammation are poorly understood. To investigate the role of plasmacytoid DC (pDC) in the initiation of autoimmune Th17- and Th1-cell responses and EAE, we depleted pDC with anti-pDC Ag-1 (anti-PDCA1) mAb prior to immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG). pDC-depleted mice developed less severe clinical and histopathological signs of EAE than control mice, which demonstrates a promoting role for pDC in the initiation of EAE. The levels of type I IFN were much lower in the sera from anti-PDCA1-treated mice. However, neutralization of type I IFN ameliorated the early phase of EAE but did not alter the severity of disease. Thus, only a minor part of the EAE-promoting effect of pDC appears to be mediated by IFN-alpha/beta secretion. The numbers of MOG-specific Th17 cells, but not Th1 cells, were lower in spleen from anti-PDCA1-treated mice compared with controls. In contrast, pDC depletion a week after MOG immunization resulted in more severe clinical signs of EAE. In conclusion, we demonstrate that pDC promote initiation of MOG-induced Th17-cell responses and EAE.
authors.affiliation: Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Isaksson
authors.forename: Brita
authors.initials: B
authors.lastname: Ardesjö
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Maija-Leena
authors.initials: ML
authors.lastname: Eloranta
authors.forename: Anna
authors.initials: A
authors.lastname: Lobell
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D015551:Autoimmunity / Q000276:immunology*; D002452:Cell Count; D002490:Central Nervous System / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D060889:Inducible T-Cell Co-Stimulator Protein; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology; D016899:Interferon-beta / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011129:Polyradiculoneuropathy; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism; D014611:Vaccination
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D016898:Interferon-alpha; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016753:Interleukin-10; D016899:Interferon-beta