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January 2008
Cutting Edge: MRF Scientists find that a specialized subset of dendritic cells could play a regulatory role in suppressing CNS inflammation and perhaps limit damage to myelin
Journal of Immunology (2008): 180:6457-6461.

Cutting Edge: CNS plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis.

Authors: Bailey-Bucktrout, S. L., S. Caulkins, G. Goings, J. A. Fischer, A. Dzionek, and S. D. Miller.

Scientific Summary: Plasmacytoid dendritic cells (pDC) have both stimulatory and regulatory affects on T cell responses, and are found in multiple sclerosis tissue. pDCs are a major CNS-infiltrating DC population during experimental autoimmune encephalomyelitis (EAE), but unlike myeloid DCs (mDC), appeared to 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 EAE resulted in exacerbation of disease severity. pDC depletion did not affect the frequency of myelin specific CD4+ T cells in peripheral lymphoid organs, but significantly enhanced CNS CD4+ T cell activation, as well as IL-17 and IFN-γ production. Moreover, CNS pDCs suppressed CNS mDC-driven production of IL-17, IFN-γ 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.

Lay Summary: This paper shows that a specialized subset of dendritic cells, called plasmacytoid DCs are present in the central nervous system of both MS patients and mice with the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Interestingly, specifically deleting these cells led to a more severe course of EAE suggesting that they play of regulatory role attempting to suppress CNS inflammation and perhaps limit damage to myelin. Experiments are continuing to determine if injecting these cells into mice with ongoing EAE could lead to an effective disease therapy.

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