Immunosuppressive effect of quercetin on dendritic cell activation and function.
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 hypersensitive diseases. Blockage of LPS-induced ERK, JNK, Akt, and NF-kappaB 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.
Huang
Ren-Yeong
RY
Graduate Institute of Medical Sciences and Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
Yu
Yen-Ling
YL
Cheng
Wan-Chien
WC
OuYang
Chun-Nan
CN
Fu
Earl
E
Chu
Ching-Liang
CL
D000818:Animals; D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D007166:Immunosuppressive Agents; D011794:Quercetin