Cutting edge: central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis.
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-gamma production. Moreover, CNS pDCs suppressed CNS myeloid dendritic cell-driven production of IL-17, IFN-gamma, 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.
Bailey-Bucktrout
Samantha L
SL
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Caulkins
Sarah C
SC
Goings
Gwendolyn
G
Fischer
Jens A A
JA
Dzionek
Andrzej
A
Miller
Stephen D
SD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology
D020381:Interleukin-17; D016753:Interleukin-10; D007371:Interferon-gamma