Orengedokuto exerts anti-allergic effects via inhibition of effector T cell activation in a murine model of contact hypersensitivity.

Abstract

Orengedokuto (OGT) is a Kampo prescription that has been used for the treatment of inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases. It is also used for the treatment of skin diseases such as urticaria and atopic dermatitis. We previously studied its anti-allergic effects of OGT on the murine model of 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying this activity remained unknown. Here, we sought to identify the mechanism involved. Using a murine model of TNCB-induced CHS, together with adoptive cell transfer experiments, we found that the anti-allergic effects of OGT may be due to the inhibition of effector T cell activation and not the induction and/or activation of regulatory T cells. Flow cytometry analysis revealed that oral administration of OGT suppressed the increase in CD8+CD44highCD62L+ cell number in draining lymph nodes (dLNs) of mice sensitized with 5% TNCB. Additionally, ex vivo experiments confirmed the suppressive effect of OGT on the activation of effector T cells, as interferon-γ (IFN-γ) production by cultured lymphocytes obtained from 5% TNCB-sensitized mice and stimulated with anti-CD3ε and anti-CD28 monoclonal antibodies was reduced by OGT administration. In conclusion, our finding suggests that OGT exerts anti-allergic effects by regulating the activation of effector T cells involved in inflammatory skin diseases such as atopic dermatitis.