Suppression of Skin Lesions by Transdermal Application of CpG-Oligodeoxynucleotides in NC/Nga Mice, a Model of Human Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by an elevation of the total IgE level in plasma, the infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in conventional conditions are known to develop skin lesions resembling human AD. We examined in this study the alterations of immune response in NC/Nga mice kept in conventional conditions, following transdermal application of CpG-oligodeoxynucleotides (ODN), which plays a critical role in immunity via the augmentation of Th1-type and suppression of Th2-type responses. CpG-ODN remarkably changed the immune response from type Th2 to Th1 as determined from cytokine mRNA and Ab levels. The serum IgE level was decreased and the expression of IgG2a was up-regulated. The application of CpG-ODN to the skin also decreased inflammatory infiltration of mast cells, and suppression in the skin lesions was observed. Furthermore, the generation of regulatory T cells, which are considered immune suppressive T cells, was observed in the skin on treatment with CpG-ODN. These results suggested CpG-ODN is effective for immunotherapy in patients with AD, which is characterized by Th2-dominated inflammation.

Dietary Supplementation with Lactic Acid Bacteria Attenuates the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice in a Strain-Dependent Manner

“…However, KW3110 also decreased both IgG1 and IgG2a levels in the plasma. These results are different from recent observations that CpG-oligodeoxynucleotides [31] and preparations from Actinidia arguta [32], which decreased IgE and IgG1 but conversely increased IgG2a. It is known that IgE and IgG1 are commonly induced by IL-4 but IgG2a is differently regulated [33, 34].…”

“…Together, these findings suggest a greater potential of KW3110 for improving the Th1/Th2 imbalance. The capacity for IL-12 activation may be particularly important because previous reports indicated that it correlated well with the improvement in AD symptoms by known pharmaceutical agents [31, 44]. In accordance with these differences in immunomodulating capacity, KW3110 mediated more pronounced effects than LGG on all the parameters tested in NC/Nga mice in vivo, including total clinical scores, blood IgE levels and immediate hypersensitivity responses.…”

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

“…Local treatment is considered preferable and acceptable for single, small, localized uncomplicated lesions in the absence of risk factors for mucocutaneous disease (45,46). The relatively high dose of 50 g of CpG was used, as it had been previously demonstrated to elicit the induction of Tregs after either systemic (28,34,47) or dermal (48,49) delivery of CpG. Notably, the downregulation of the immune and inflammatory responses and the induction of Treg activity have been recently shown in this model to ameliorate disease (17).…”

“…Further, the use of immunomodulators in conjunction with topical drugs has the potential to reduce the amount of drug required to achieve healing. Lipid-based or other transcutaneous delivery systems have been reported for administration of CpG and may have potential for treatment in patients (48,49,92). CpG may prove to be an effective alternative treatment or coadjuvant that could be used either independently or in combination with lower doses of standard chemotherapeutic drugs for the treatment of cutaneous leishmaniasis caused by L. (V.) panamensis.…”

Therapeutic Effects of Gyokuheifusan on NC/Nga Mouse Model of Allergic Dermatitis

“…1) It has a complex and chronic pathogenesis that provides many potential cellular and molecular targets for therapeutic intervention, but may also include redundant pathways. 2) In addition, although corticosteroids and calcineurin inhibitors are used in the treatment of AD, 3,4) they remain only palliative.…”