Del-1 is an endogenous endothelial-derived inhibitor of LFA-1-mediated leukocyte adhesion (Choi et al. Science 2008). As Del-1 has high expression in brain, we assessed here its role in neuroinflammation in experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis. We found decreased Del-1 expression in the inflamed spinal cord of mice subjected to the EAE protocol. Moreover, Del-1-deficiency in mice resulted in increased EAE severity, associated with increased inflammatory cell recruitment to the inflamed spinal cord. Immunohistochemistry showed that demyelination and axonal damage of the spinal cord was higher due to Del-1-deficiency. Recently, we proved that Del-1 suppressed IL-17-triggered inflammation (Eskan et al., Nat Immunol, 2012). Consistent with this finding, we found that the infiltration of IL-17 producing CD4+ T cells (Th17 cells) was significantly increased at the onset of the disease. This resulted in enhanced infiltration of CD45highCD11b+ monocytes/macrophages that was up to the effector phase of EAE. Subsequent studies revealed that IL17R-/- deficiency reversed the aggravated EAE phenotype of Del-1-deficiency, accompanied by a decrease of leukocyte infiltration into the spinal cord. Our results suggest that Del-1 deficiency exacerbates EAE disease severity by elevating Th17 cell infiltration to the inflamed spinal cord, which implies that Del-1 could be used as a therapeutic approach for neuro-inflammatory disorders.
- Copyright © 2013 by The American Association of Immunologists, Inc.