Dendritic Cell Activation and Function Immunosuppressive Effect of Quercetin on

Dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity. Thus, DCs have been regarded as a major target of immunosuppressants for the control of harmful immune responses. In this study, we examined the effect of quercetin, a natural flavonoid found in many vegetables and fruits, on the activation and function of mouse DCs. 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 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, coadministration of quercetin with 2,4-dinitro-1-fluorobenzene prevented 2,4-dinitro-1-fluorobenzene–induced contact hypersensitivity, indicating the potential of quercetin for treating delayed-type hyper-sensitive diseases. Blockage of LPS-induced ERK, JNK, Akt, and NF-kB 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. D endritic cells (DCs), which are the most potent APCs, are critical sentinels of the immune system and have the unique ability to integrate a wide array of incoming signals and convey them to lymphocytes, thus directing the appropriate immune responses against microbial pathogens and tumors (1). After encountering pathogen-associated molecular patterns , DCs become mature to enhance the expression of MHC class II and accessory molecules and produce cytokines and che-mokines (2). TLRs are the major pattern recognition receptors in DCs and initiate DC function to regulate immune responses via various signaling pathways (3). Thus, the use of DCs to control cancer and infectious diseases has been proposed (4). However, DCs are also involved in the pathogenesis of several diseases caused by immune dysfunction, such as chronic inflammation and autoimmunity (5, 6). Substances downregulating DC activation can potentially be applied to the treatment of these diseases. Traditionally, natural products represent a source for discovering bioactive drugs, including immunomodulators, in the pharmaceutical industry (7). Flavonoids are natural products from many vegetables, fruits, herbs, flowers, seeds, and beverages that are present in diet (8). They are polyphenolic compounds and display a variety of biological effects, such as antioxidation, anti-inflammation, anticancer, gastroprotection, cardiovascular protection, oral protection , and memory improvement …