CD11cCD88CD317 myeloid cells are critical mediators of persistent CNS autoimmunity.

Natalizumab, a humanized monoclonal antibody (mAb) against α4-integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of α4-integrin in CD11c cells should curtail their migration to the central nervous system (CNS) and ameliorate experimental autoimmune encephalomyelitis (EAE). We generated CD11c.

Limitations of cell-lineage-specific non-dynamic gene recombination in CD11c.CreITGA4 mice.

Background: The Cre-lox system is a non-dynamic method of gene modification and characterization. Promoters thought to be relatively cell-specific are utilized for generation of cell-lineage-specific gene modifications.

Methods: CD11c.

α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model.

Objective: The goal of this study was to investigate the role of CD 19 B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19 B cells outside the CNS drive inflammation in EAE.

Methods: We generated CD19.

TLR3 agonism re-establishes CNS immune competence during 4-integrin deficiency.

Objective: Natalizumab blocks 4-integrin-mediated leukocyte migration into the central nervous system (CNS). It diminishes disease activity in multiple sclerosis (MS), but carries a high risk of progressive multifocal encephalopathy (PML), an opportunistic infection with JV virus that may be prompted by diminished CNS immune surveillance. The initial host response to viral infections entails the synthesis of type I interferons (IFN) upon engagement of TLR3 receptors.