title: Distinct modulation of human myeloid and plasmacytoid dendritic cells by anandamide in multiple sclerosis.
abstract: OBJECTIVE
  The immunopathogenesis of multiple sclerosis (MS) has always been thought to be driven by chronically activated and autoreactive Th-1 and Th-17 cells. Recently, dendritic cells (DCs) have also been thought to significantly contribute to antigenic spread and to maturation of adaptive immunity, and have been linked with disease progression and exacerbation. However, the role of DCs in MS pathogenesis remains poorly understood.
  
  
  METHODS
  We compared the level of cytokine production by myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in healthy subjects and MS patients, following in vitro stimulation of Toll-like receptors 7/8. We also evaluated the effect of the main endocannabinoid, anandamide (AEA), in these DC subsets and correlated cytokine levels with defects in the endocannabinoid system.
  
  
  RESULTS
  mDCs obtained from MS patients produce higher levels of interleukin-12 and interleukin-6, whereas pDCs account for lower levels of interferon-α compared to healthy subjects. AEA significantly inhibited cytokine production from healthy mDCs and pDCs, as well as their ability to induce Th-1 and Th-17 lineages. Moreover, we found that in MS only pDCs lack responsiveness to cytokine inhibition induced by AEA. Consistently, this specific cell subset expresses higher levels of the anandamide hydrolase fatty acid amide hydrolase (FAAH).
  
  
  CONCLUSIONS
  Our data disclose a distinct immunomodulatory effect of AEA in mDCs and pDCs from MS patients, which may reflect an alteration of the expression of FAAH, thus forming the basis for the rational design of new endocannabinoid-based immunotherapeutic agents targeting a specific cell subset.
authors: Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
authors: Valerio
authors: V
authors: Chiurchiù
authors: Maria Teresa
authors: MT
authors: Cencioni
authors: Elisa
authors: E
authors: Bisicchia
authors: Marco
authors: M
authors: De Bardi
authors: Claudio
authors: C
authors: Gasperini
authors: Giovanna
authors: G
authors: Borsellino
authors: Diego
authors: D
authors: Centonze
authors: Luca
authors: L
authors: Battistini
authors: Mauro
authors: M
authors: Maccarrone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D063388:Endocannabinoids; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D016207:Cytokines; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D000099252:Fatty Acid Amide Hydrolases; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C078814:anandamide