Aryl hydrocarbon receptor signals in epithelial cells govern the recruitment and location of Helios+ Tregs in the gut

Yusuke Yoshimatsu, Tomohisa Sujino, Kentaro Miyamoto, Yosuke Harada, Shun Tanemoto, Keiko Ono, Satoko Umeda, Kosuke Yoshida, Toshiaki Teratani, Takahiro Suzuki, Yohei Mikami, Nobuhiro Nakamoto, Nobuo Sasaki, Kaoru Takabayashi, Naoki Hosoe, Haruhiko Ogata, Kazuaki Sawada, Takeshi Imamura, Akihiko Yoshimura, Takanori Kanai

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

CD4+Foxp3+ regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II+ ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25+ T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios+ Tregs in the colon.

Original languageEnglish
Article number110773
JournalCell Reports
Volume39
Issue number6
DOIs
Publication statusPublished - 2022 May 10

Keywords

  • aryl hydrocarbon receptor
  • CP: Immunology
  • MHC class II epithelial cells
  • regulatory T cells
  • ulcerative colitis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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