title: Dendritic Cells Modulate Iron Homeostasis and Inflammatory Abilities Following Quercetin Exposure.
abstract: Fruits and vegetables are rich in plant polyphenols, whose consumption is encouraged in healthy dietary regimes due to their antioxidants and anti-inflammatory effects. These organic molecules exhibit numerous properties including phylochelation; the ability to complex metal ions, including highly reactive iron. Among polyphenols, we focused our attention on quercetin that previously demonstrated its ability to reduce dendritic cells (DCs) inflammatory cytokine secretion and antigen presentation following LPS exposure. Dendritic cell inflammatory response is also associated with modulation of several iron metabolism related genes.
  
  
  
  To characterize the axis between quercetin exposure and iron extracellular transport that may explain polyphenol anti-inflammatory abilities.
  
  
  
  Bone marrow derived DCs were exposed to 25μM of quercetin on day 7 and treated with 1 μg/mL of LPS on day 8. The relation between quercetin exposure and the expression level of genes involved in iron homeostasis was addressed by qPCR. The axis between iron export and quercetin exposure was confirmed in vitro and in vivo using quercetin gavage and quercetin-enriched diet.
  
  
  
  Here we demonstrate that DCs, exposed to quercetin, activate a pattern of genes that increase extracellular iron export, resulting in an overall decrease in the intracellular iron content and consequent diminished inflammatory abilities. This DCs phenotype is consistent with anti-inflammatory phenotype of the mucosal resident DCs, the ones most commonly exposed to polyphenols.
  
  
  
  Iron balance is a crucial checkpoint for DCs inflammatory abilities. Quercetin-enriched nutritional regimes that favor DCs extracellular iron transport could reduce the incidence of chronic inflammatory syndromes.
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Galleggiante
authors.affiliation: Institute of Sciences of Food Production C.N.R., Unit of Lecce, via Monteroni, 73100, Lecce, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Santis
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cavalcanti
authors.affiliation: Institute of Sciences of Food Production C.N.R., Unit of Lecce, via Monteroni, 73100, Lecce, Italy.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Scarano
authors.affiliation: Institute of Sciences of Food Production C.N.R., Unit of Lecce, via Monteroni, 73100, Lecce, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Benedictis
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Serino
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Caruso
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Mastronardi
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.affiliation: European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.affiliation: University of Tasmania, School of Health Sciences, Launceston, Tasmania. Australia.
authors.forename: Dale
authors.initials: D
authors.lastname: Kunde
authors.affiliation: Institute of Sciences of Food Production C.N.R., Unit of Lecce, via Monteroni, 73100, Lecce, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Santino
authors.affiliation: National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Chieppa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D011794:Quercetin; D007501:Iron
keywords: Dendritic cells; inflammation; iron; mucosal immunology; nutrition.; quercetin