Research Article: Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model

Date Published: January 20, 2017

Publisher: Public Library of Science

Author(s): Yuka Nagata, Takeshi Yamamoto, Michie Hayashi, Shusaku Hayashi, Makoto Kadowaki, Hossam M Ashour.


Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT. The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount. Allergic symptoms decreased in the OIT-treated FA mice. OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased the level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma. Moreover, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, and the combination therapy further suppressed the Th2 immune responses and the mast cell degranulation. In addition, OIT significantly increased the population of Foxp3+ CD4+ regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto. Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon. These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment.

Partial Text

Food allergies (FAs) represent an increasingly prevalent human health problem that affects a large proportion of the general population in developed countries [1]. Up to 8% of children and 5% of adults self-reported an allergy to at least 1 food [1, 2]. Despite the increasing prevalence of FA, therapeutic options remain limited [3, 4]. No treatments have been proven to accelerate the development of oral tolerance or to provide effective protection from accidental exposure. The current standard management relies on antigen avoidance and emergency preparedness [4, 5].

The effectiveness of OIT for FA has been demonstrated in human patients [8–13]; however, the current therapeutic efficacy of OIT is not satisfactory, and the underlying mechanisms have not been elucidated.