title: Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells.
abstract: The functions of dendritic cells (DCs) are impaired in patients with liver cirrhosis. It is well-known that cirrhotic patients show decreased levels of plasma branched-chain amino acids (BCAA). Although amino acids are associated with maintaining the cell structure and function in many organs, limited data are available regarding the role of amino acids including BCAA in the immune system. We aimed to investigate the roles of BCAA in the function of human monocyte-derived DCs (MoDC). CD14-positive monocytes (CD14 (+)) were isolated from PBMC from healthy volunteers and hepatitis C virus (HCV) cirrhotic patients. In medium deprived of BCAA or valine, monocytes were able to differentiate into immature, but not into mature, DCs and showed weak expression of CD83. The deprivation of leucine or isoleucine did not affect this process. The MoDC allostimulatory capacity was significantly decreased in medium deprived of BCAA or valine (p = 0.017, p = 0.012, Bonferroni's analysis, respectively). Annexin V(FITC)/propidium iodide staining showed that the DC yield and viability were not significantly different under any medium. Immunoblotting demonstrated that depletion of valine or leucine decreased phospho-S6 kinase expression. Valine increased dose-dependently the allostimulatory capacity and IL-12 production of MoDC from both healthy volunteers and HCV cirrhotic patients. An elevated extracellular concentration of valine could improve the DC function in cirrhotic patients. These data provide a rationale for nutrition therapy that could be beneficial to patients with cirrhosis.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Noriatsu
authors.initials: N
authors.lastname: Kanno
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000096:biosynthesis / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000178:diet therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000276:immunology; D008103:Liver Cirrhosis / Q000150:complications / Q000178:diet therapy / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019893:Ribosomal Protein S6 Kinases / Q000276:immunology / Q000378:metabolism; D014633:Valine / Q000494:pharmacology* / Q000627:therapeutic use; D000097802:CD83 Antigen
chemical_list: D017304:Annexin A5; D015703:Antigens, CD; D007136:Immunoglobulins; D018664:Interleukin-12; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D019893:Ribosomal Protein S6 Kinases; D014633:Valine; D000097802:CD83 Antigen