Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice

Takaaki Kawaguchi, Maiko Mori, Keiko Saito, Yasuyo Suga, Masaki Hashimoto, Minako Sako, Naoki Yoshimura, Michihide Uo, Keiko Danjo, Yuka Ikenoue, Kaori Oomura, Junko Shinozaki, Akira Mitsui, Takayuki Kajiura, Manabu Suzuki, Masakazu Takazoe

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17 Citations (Scopus)

Abstract

Background: In Crohn’s disease (CD), the involvement of food antigens in immune responses remains unclear. The objective of this study was to detect immune responses against food antigens in CD patients and examine the mechanism in a mouse model of colitis. Methods: We enrolled 98 CD patients, 50 ulcerative colitis patients, and 52 healthy controls (HCs) to compare the levels of serum immunoglobulin (Ig)Gs against 88 foods. The presence of serum IgGs against foods was also examined in interleukin (IL)-10 knockout (KO) mice in which CD4+ T cell activation by antigenic food protein was assessed. Mice transferred with IL-10 KO cells received diets with or without food antigens, and the development of colitis was evaluated. Results: The prevalence of IgGs against various foods, especially vegetables, grains, and nuts, was significantly higher in CD patients than in HCs. Similarly, the prevalence of IgGs against food proteins was higher in IL-10 KO mice than in BALB/c mice. Beta-conglycinin, identified as an antigenic food proteins in IL-10 KO mice, induced CD4+ T cell production of interferon-γ and IL-17 through dendritic cell antigen presentation. Elimination of the food antigens ameliorated the development of colitis in mice without altering the composition of their intestinal microbiota. Conclusions: In CD colitis mice, intestinal inflammation via CD4+ T cell hyperactivation was induced by food antigens associated with high serum IgG levels and was ameliorated by the elimination of food antigens. This disrupted immunological tolerance to food antigen, which might act as an exacerbating factor, remains to be elucidated in CD patients.

Original languageEnglish
Pages (from-to)394-405
Number of pages12
JournalJournal of gastroenterology
Volume50
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

Keywords

  • CD4 T cell
  • Crohn’s disease
  • Experimental colitis
  • Food antigens
  • Serum immunoglobulin G

ASJC Scopus subject areas

  • Gastroenterology

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    Kawaguchi, T., Mori, M., Saito, K., Suga, Y., Hashimoto, M., Sako, M., Yoshimura, N., Uo, M., Danjo, K., Ikenoue, Y., Oomura, K., Shinozaki, J., Mitsui, A., Kajiura, T., Suzuki, M., & Takazoe, M. (2015). Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice. Journal of gastroenterology, 50(4), 394-405. https://doi.org/10.1007/s00535-014-0981-8