Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE
2009 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 39, no 10, 2925-2935 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2009. Vol. 39, no 10, 2925-2935 p.
Autoimmunity, DC, EAE/MS, T cells, Type I IFN
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-108362DOI: 10.1002/eji.200839179ISI: 000271151000030PubMedID: 19637225OAI: oai:DiVA.org:uu-108362DiVA: diva2:235564