Friday, February 1
st
- h 2:00 p.m.
Seminars Room, NICO
Giovanni Ferrara, PhD
Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili (DINOGMI), Università di Genova
Does Nerve-glial antigen 2 (NG2) play a role in dendritic cell activation?
Nerve/glial-antigen 2 (NG2), expressed by oligodendrocyte progenitor cells (OPC), essential for remyelination, and by pericytes, crucial for blood-brain-barrier (BBB) integrity, could be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). We found that, in addition to macrophages, NG2 is expressed on T cells and dendritic cells (DC) in naïve WT mice.
We described that induction of EAE with myelin oligodendrocyte glycoprotein (MOG35-55) in NG2 knock-out (NG2KO) mice results in a milder EAE than in wild-type (WT) mice with less intense neuropathology associated with improvement in blood-brain barrier. Chimera experiments confirmed the significant role of NG2 expressed by immune cells in EAE: mice reconstituted with NG2KO bone marrow cells develop a milder EAE, regardless of their inherent WT or NG2KO genotype.
Further characterization, demonstrated that, upon MOG35–55-specific recall response of NG2KO T cells in the presence of DCs lacking NG2, is associated with a shift towards a less proinflammatory cytokine profile, with significantly less IFN-γ, but more IL-4 and IL-10. We therefore analyzed MOG-primed lymph node cells for their intracellular expression of IL-12 and we demonstrated that the proportion of IL-12-expressing DCs was significantly lower in NG2KO-affected mice, indicating that NG2KO DCs skew MOG-specific T cell response to an anti-inflammatory Th2 type.
In addition, preliminary data, showed that NG2 is induced upon pro-inflammatory stimulation of DCs. Our data suggest that NG2 plays a role in EAE not only at CNS/BBB level, but also impacting on DC activation and thereby their stimulation of reactive T cells, through controlling IL-12 expression.
Host: Enrica Boda
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