Retinoic acid contributes to the induction of IL-12-hypoproducing dendritic cells

Yasuyo Wada, Tadakazu Hisamatsu, Nobuhiko Kamada, Susumu Okamoto, Toshifumi Hibi

研究成果: Article査読

40 被引用数 (Scopus)


Background: Vitamin A is an important regulator of the human immune system, especially in the gut. Recent studies have revealed that retinoic acid (RA) in gut-associated dendritic cells (DCs) enhances the transforming growth factor (TGF)-β-dependent conversion of naïve T cells into regulatory T (Treg) cells. Thus, RA produced by DCs contributes to immune tolerance mechanisms in the gut. In the present study we focused on the effect of RA on the differentiation of the DC, and tried to clarify the role of DCs induced by RA in a murine colitis model. Methods: Human peripheral blood CD14+ monocytes were cultured with granulocyte-macrophage colony stimulation factor and interleukin (IL)-4, with or without synthetic RA, Am80. Differentiated DCs cultured with Am80 (Am-DCs) were compared with conventional monocyte-derived DCs (cDCs). Results: Am-DCs showed macrophage (M/)-like adherent phenotypes, and lacked the expression of the typical DC marker CD1a. Am-DCs produced less IL-12p70 and revealed less polarizing ability toward type 1 helper T cells (Th1) by allogeneic mixed lymphocyte reaction with naïve T cells. In addition, Am80 treatment ameliorated macro- and microscopic damage in dextran sodium sulfate-induced colitis in mice, and suppressed the colitis-induced elevation of IL-12 in the intestinal lamina propria. Conclusions: RA might play an important role in gut immune tolerances via local generation of IL-12 hypoproductive DCs. RA may be a useful clinical treatment for Th1-mediated inflammatory diseases, especially those such as Crohn's disease occurring in the gut.

ジャーナルInflammatory bowel diseases
出版ステータスPublished - 2009 11 26

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 消化器病学


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