Dendritic cells modulate iron homeostasis and inflammatory abilities following quercetin exposure

Background: 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. Objective: To characterize the axis between quercetin exposure and iron extracellular transport that may explain polyphenol anti-inflammatory abilities. Method: 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. Results: 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. Conclusions: 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.