Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in NC/Nga mice.
OBJECTIVE
CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and the suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to a tape-stripped skin of NC/Nga mouse, a human atopic dermatitis (AD) model, by evaluating the production of cytokines and immunoglobulin isotypes.


METHODS
Model antigen, ovalbumin (OVA), and CpG-ODN were applied on to the shaved skin. The penetration of OVA and CpG-ODN was evaluated using confocal laser scanning microscopy (CLSM). Secretion of cytokine from splenocytes and changes in immunoglobulin isotype levels were determined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Through CLSM it was revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Coadministration of CpG-ODN and OVA to the skin elicited an antigen-specific, Th1-predominant immune response and enhanced the production of IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. In terms of antigen-specific antibody production, the level of IgG2a regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed.


CONCLUSIONS
Administration of CpG-ODN with antigen through the skin may shift the immune response from a Th2- to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases such as 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, aramaki@ps.toyaku.ac.jp.
Yotsumoto
Satoshi
S
Sakamoto
Takatoshi
T
Tsuchiya
Seishi
S
Aramaki
Yukihiko
Y
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000287:Administration, Topical; D000818:Animals; D000906:Antibodies / Q000097:blood; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology*; D012882:Skin Tests; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000941:Antigens; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin