Induction of Regulatory T Cells as a Novel Mechanism Underlying the Therapeutic Action of Kakkonto, a Traditional Japanese Herbal Medicine, in a Murine Food Allergy Model.
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.
Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Takeshi
T
Yamamoto
Kanae
K
Fujiwara
Yuma
Y
Tsubota
Natsuko
N
Kageyama-Yahara
Shusaku
S
Hayashi
Makoto
M
Kadowaki
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005512:Food Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D029001:Herbal Medicine; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D004365:Drugs, Chinese Herbal; C090831:kakkon-to; D010047:Ovalbumin