期刊
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
卷 169, 期 3, 页码 146-156出版社
KARGER
DOI: 10.1159/000445433
关键词
Food allergy; Regulatory T cells; Traditional herbal medicine; Kakkonto; Intestinal mucosal immunity; Animal models
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [25460891, 24590879]
- Joint Usage/Research Center for Science-Based Natural Medicine Institute of Natural Medicine, University of Toyama
- Grants-in-Aid for Scientific Research [16H05276, 24590879, 25460891] Funding Source: KAKEN
Background: The number of patients with food allergy (FA) has dramatically increased. Although satisfactory drug therapies for FA are not available, we have found that kakkonto, a traditional Japanese herbal medicine, suppressed the occurrence of allergic symptoms in an FA mouse model. Thus, we investigated whether kakkonto could regulate the activation and differentiation of T cells in the colon. Methods: BALB/c mice were systemically sensitized and then orally challenged with ovalbumin. FA mice were orally treated with kakkonto. Lamina propria (LP) cells from their colons were isolated and analyzed. Results: Kakkonto significantly reduced the proportion of CD69(+) cells and the elevated helper T cell type 2-specific transcription factor GATA-3 mRNA expression in the LP CD4(+) T cells, showing that kakkonto has a suppressive effect on the activation and Th2 differentiation of LP effector CD4(+) T cells of the FA mouse colon. Furthermore, kakkonto significantly increased the proportion of Foxp3(+)CD4(+) regulatory T cells in the LP CD4(+) T cells of the FA mouse colon. Similarly, the number of Foxp3-positive cells was dramatically increased in the colonic mucosa of kakkonto-administered FA mice. However, the pharmacological effect and Foxp3(+)CD4(+) regulatory T cell-inducing ability of kakkonto were not attenuated by the administration of an anti-CD25 monoclonal antibody in the FA model. Conclusions: The induction of Foxp3(+)CD4(+)CD25(-) regulatory T cells in the colon as a novel mechanism underlying the therapeutic action of kakkonto could be utilized for the development of a novel anti-FA drug. (C) 2016 S. Karger AG, Basel
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