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Cutting Edge: Central Nervous System Plasmacytoid Dendritic Cells Regulate the Severity of Relapsing Experimental Autoimmune Encephalomyelitis¹

Samantha L. Bailey-Bucktrout^*, Sarah C. Caulkins^*, Gwendolyn Goings^*, Jens A. A. Fischer, Andrzej Dzionek and Stephen D. Miller^2,*

^* Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and Miltenyi Biotec, Bergisch Gladbach, Germany

Plasmacytoid dendritic cells (pDCs) have both stimulatory and regulatory effects on T cells. pDCs are a major CNS-infiltrating dendritic cell population during experimental autoimmune encephalomyelitis but, unlike myeloid dendritic cells, have a minor role in T cell activation and epitope spreading. We show that depletion of pDCs during either the acute or relapse phases of experimental autoimmune encephalomyelitis resulted in exacerbation of disease severity. pDC depletion significantly enhanced CNS but not peripheral CD4⁺ T cell activation, as well as IL-17 and IFN- production. Moreover, CNS pDCs suppressed CNS myeloid dendritic cell-driven production of IL-17, IFN-, and IL-10 in an IDO-independent manner. The data demonstrate that pDCs play a critical regulatory role in negatively regulating pathogenic CNS CD4⁺ T cell responses, highlighting a new role for pDCs in inflammatory autoimmune disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by U.S. Public Health Service, National Institutes of Health Research Grant NS-030871, National Multiple Sclerosis Society (NMSS) Research Grant RG 3793-A-7, NMSS Postdoctoral Fellowship Grant FG 1563 A-1 (to S.L.B.), and a grant from the Myelin Repair Foundation.

² Address correspondence and reprint requests to Dr. Stephen D. Miller, Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611. E-mail address: s-d-miller{at}northwestern.edu

³ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; DC, dendritic cell; LN, lymph node; mDC, myeloid DC; mPDCA, mouse plasmacytoid dendritic cell antigen-1; MS, multiple sclerosis; 1-MT, 1-methyl-D-tryptophan; pDC, plasmacytoid DC; PLP_139–151, proteolipid protein peptide 139–151; R-EAE, relapsing EAE; Treg, regulatory T cell.