CNS-resident classical DCs play a critical role in CNS autoimmune disease

The Journal of Clinical Investigation
David A GilesBenjamin M Segal

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS), induced by the adoptive transfer of myelin-reactive CD4+ T cells into naive syngeneic mice. It is widely used as a rodent model of multiple sclerosis (MS). The development of EAE lesions is initiated when transferred CD4+ T cells access the CNS and are reactivated by local antigen-presenting cells (APCs) bearing endogenous myelin peptide/MHC class II complexes. The identity of the CNS-resident, lesion-initiating APCs is widely debated. Here we demonstrate that classical dendritic cells (cDCs) normally reside in the meninges, brain, and spinal cord in the steady state. These cells are unique among candidate CNS APCs in their ability to stimulate naive, as well as effector, myelin-specific T cells to proliferate and produce proinflammatory cytokines directly ex vivo. cDCs expanded in the meninges and CNS parenchyma in association with disease progression. Selective depletion of cDCs led to a decrease in the number of myelin-primed donor T cells in the CNS and reduced the incidence of clinical EAE by half. Based on our findings, we propose that cDCs, and the factors that regulate them, be further investigat...Continue Reading

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Apr 23, 2019·Annals of the New York Academy of Sciences·Vincent GeenenHenri Martens
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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
transgenic
CLIP
PMA
PCR

Software Mentioned

R
GraphPad Prism
FlowJo
nSolver Analysis
Fluoview

Related Concepts

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