Inflammatory role of dendritic cells in Amyotrophic Lateral Sclerosis revealed by an analysis of patients’ peripheral blood

Abstract

Chronic inflammation is one of the causes of neurodegeneration in Amyotrophic lateral sclerosis (ALS). Here we examined whether circulating dendritic cells (DCs) can contribute to disease progression. We found ALS patients show a significant reduction in the number of circulating DCs. Also, patients’ DCs present an increased expression of CD62L and a tendency to overexpress CCR2 compared with healthy donors. Moreover, DCs derived from a subpopulation of ALS patients produced higher levels of IL-8 and CCL-2 upon lipopolysaccharide (LPS)-stimulation. Finally, we found a significant inverse correlation between the time from onset of the pathology to its diagnosis and the levels of IL-6 secretion induced by LPS. Our data support the hypothesis, in a subpopulation of patients, DCs recruited at the diseased tissue produce high levels of CCL-2 and IL-8 and contribute to the inflammatory process promoting the recruitment of other inflammatory cells. An increased efficiency of IL-6 production may accelerate only the initial phases of disease progression. Blood DC analysis can be used to identify ALS patients with an altered course of inflammatory cell recruitment at the diseased central nervous system (CNS). The high levels of CD62L expression suggests this molecule could be a target for treatment of CNS inflammation.