Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice.
CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to tape-stripped mouse skin by evaluating the production of cytokines and Ig isotypes. Confocal laser scanning microscopy revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Co-administration of CpG-ODN and OVA to the disrupted skin elicited an antigen-specific Th1-predominant immune response and enhanced the production of Th1-type cytokines, IL-12 and IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. Cytokine production was supported by the expression of mRNA in the draining lymph node. In terms of antigen-specific antibody production, the level of IgG2a which is regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed. Furthermore, administration of CpG-ODN via the skin drastically attenuated the production of IgE in mice undergoing IgE-type immune response. Administration of CpG-ODN through the skin may shift the immune response from Th2 to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases like AD, which is characterized by Th2-dominated inflammation.
Inoue
Joe
J
School of Pharmacy, Tokyo University of Pharmacy and Life Science 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Yotsumoto
Satoshi
S
Sakamoto
Takatoshi
T
Tsuchiya
Seishi
S
Aramaki
Yukihiko
Y
D000276:Adjuvants, Immunologic; D000287:Administration, Topical; D000818:Animals; D000906:Antibodies / Q000032:analysis; D000918:Antibody Specificity; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012869:Skin Absorption / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000941:Antigens; D016207:Cytokines; D009841:Oligonucleotides; D012333:RNA, Messenger; D010047:Ovalbumin