Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function

• Main Authors: Ren-Yeong Huang, 黃仁勇
• Other Authors: Eearl Fu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/93981928264928878815

博士 === 國防醫學院 === 醫學科學研究所 === 98 === Dendritic cells (DCs) are professional antigen presenting cells play a crucial role in the immune sentinels as initiators of T cell responses against microbial pathogens and tumors as well as inflammation, thus bridging innate and adaptive immunity. DCs have been regarded as a major target of immunosuppressants for the control of harmful immune responses. In this study, the effect of quercetin, a natural flavonoid found in many vegetables and fruits, on the differentiation, activation and function of mouse DCs was examined. First, the differentiation of DCs from bone marrow precursor cells was not dampened by quercetin at notoxic concentration. Quercetin effectively inhibited LPS-induced DC activation by reducing the production of proinflammatory cytokines/chemokines and the expression levels of MHC class II and costimulatory molecules. In addition, quercetin uniquely blocked the endocytosis by DCs and the LPS-induced DC migration was diminished by quercetin treatment. Furthermore, quercetin abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, both in vitro and in vivo. Remarkably, co-administration of quercetin with 2,4-dinitro-1-fluorobenzene (DNFB) prevented DNFB-induced contact hypersensitivity, indicating the potential of quercetin for treating delay-type hypersensitive diseases. Blockage of LPS-induced ERK, JNK, Akt, and NF-κB activation contributed to the inhibitory effect of quercetin on DCs. These results strongly suggest that quercetin may be a potent immunosuppressive agent and could be used in the prevention and therapy of chronic inflammation, autoimmunity, and transplantation via the abolishment of DC activation and function.