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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1548-1556
Number of pages9
JournalInflammatory Bowel Diseases
Volume15
Issue number10
DOIs
Publication statusPublished - 2009

    Fingerprint

Keywords

  • Dendritic cells
  • DSS colitis mouse
  • IL-12
  • RAR agonist
  • Retinoic acid

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this