Oral administration of paeoniflorin attenuates allergic contact dermatitis by inhibiting dendritic cell migration and Th1 and Th17 differentiation in a mouse model.
Allergic contact dermatitis (ACD) is a hapten-specific CD4(+) T-cells mediated inflammatory response of the skin. Its pathomechanism involves 2 phases, an induction phase and an elicitation phase. Langerhans cells (LCs) and dendritic cells (DCs) in the skin play key roles in presenting low molecular weight chemicals (haptens) to the lymph nodes. Therefore, inhibition of the migration of LCs or DCs and T-cell proliferation is each expected to control ACD disease. To explore the effectiveness of paeoniflorin (PF) on the migration of LCs and T-cell proliferation in vivo, we establish a murine model of ACD, promoted by repeated exposure to an allergen (specifically 1-Chloro-2,4-dinitrobenzene (DNCB)). Administration of PF inhibits DC migration in this DNCB-induced model in the induction phase. As a result, epidermal LC density in the elicitation phase increased in PF-treated mice when compared to PF-untreated mice. At the same time, PF reduced IFN-γ(+)CD4(+) and IL-17(+)CD4(+) T cells proliferation (but not IL-4(+)CD4(+) T cells proliferation), leading to an attenuated cutaneous inflammatory response. Consistent with this T-cell proliferation profile, secretions of IFN-γ and IL-17 were reduced and IL-10 secretion increased in PF-treated mice, but production of IL-4 and IL-5 remained unchanged in the skin and blood samples. These results suggest that oral administration of PF can treat and prevent ACD effectively through inhibition of DC migration, and thus decrease the capacity of DCs to stimulate Th1 and Th17 cell differentiation and cytokine production.
Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China; Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
Dongmei
D
Shi
Department of Ultrasonography, Jining No. 1 People's Hospital, Shandong, PR China.
Xuefeng
X
Li
Georgetown University Medical Center, Washington D.C., USA.
Dongmei
D
Li
Department of Pathology, Jining No. 1 People's Hospital, Shandong, PR China.
Quanjing
Q
Zhao
Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
Yongnian
Y
Shen
Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
Hongxia
H
Yan
Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China.
Hongjun
H
Fu
Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
Hailin
H
Zheng
Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.
Guixia
G
Lu
Department of Dermatology, Jining No. 1 People's Hospital, Shandong, PR China. Electronic address: qiou_ying@sohu.com.
Ying
Y
Qiu
Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China. Electronic address: liumyco@hotmail.com.
Weida
W
Liu
D000284:Administration, Oral; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004137:Dinitrochlorobenzene; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects*; D006027:Glycosides
D016207:Cytokines; D004137:Dinitrochlorobenzene; D005960:Glucosides; D039821:Monoterpenes; D012333:RNA, Messenger; C015423:peoniflorin; D006027:Glycosides
1-chloro-2,4-dinitrobenzene; Allergic contact dermatitis; Contact sensitivity; Dendritic cells; Paeoniflorin