Distinct modulation of human myeloid and plasmacytoid dendritic cells by anandamide in multiple sclerosis

摘要: OBJECTIVE: The immunopathogenesis of multiple sclerosis (MS) has always been thought to be driven by chronically activated and autoreactive Th-1 Th-17 cells. Recently, dendritic cells (DCs) have also significantly contribute antigenic spread maturation adaptive immunity, linked with disease progression exacerbation. However, the role DCs in MS pathogenesis remains poorly understood. METHODS: We compared level cytokine production myeloid (mDCs) plasmacytoid (pDCs) healthy subjects patients, following vitro stimulation Toll-like receptors 7/8. We evaluated effect main endocannabinoid, anandamide (AEA), these DC subsets correlated levels defects endocannabinoid system. RESULTS: mDCs obtained from patients produce higher interleukin-12 interleukin-6, whereas pDCs account for lower interferon-α subjects. AEA inhibited mDCs pDCs, as well their ability induce lineages. Moreover, we found that only lack responsiveness inhibition induced AEA. Consistently, this specific cell subset expresses hydrolase fatty acid amide (FAAH). INTERPRETATION: Our data disclose a distinct immunomodulatory which may reflect an alteration expression FAAH, thus forming basis rational design new endocannabinoid-based immunotherapeutic agents targeting subset.