@article{d685260b6de94307a611ca6b3e66a16e,
title = "Aryl hydrocarbon receptor signals in epithelial cells govern the recruitment and location of Helios+ Tregs in the gut",
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.",
keywords = "CP: Immunology, MHC class II epithelial cells, aryl hydrocarbon receptor, regulatory T cells, ulcerative colitis",
author = "Yusuke Yoshimatsu and Tomohisa Sujino and Kentaro Miyamoto and Yosuke Harada and Shun Tanemoto and Keiko Ono and Satoko Umeda and Kosuke Yoshida and Toshiaki Teratani and Takahiro Suzuki and Yohei Mikami and Nobuhiro Nakamoto and Nobuo Sasaki and Kaoru Takabayashi and Naoki Hosoe and Haruhiko Ogata and Kazuaki Sawada and Takeshi Imamura and Akihiko Yoshimura and Takanori Kanai",
note = "Funding Information: We thank Chiemi Ido, Ena Nomura, Yuzo Koda, Hiroki Kiyohara, Nobuhito Taniki, Koji Okabayashi (Keio University), Daniel Mucida (The Rockefeller University), Mariya London (New York University), Shohei Hori (Tokyo University), Takatoshi Chinen (Kyushu University), and Tsudoi Miyamoto for their discussion and reading of the manuscript and the JKic, Keio core facility for helping with multi-photon microscopy. We thank Melissa Crawford, PhD, from Edanz ( https://jp.edanz.com/ac ) for editing a draft of this manuscript. Grants-in-Aid from the Japanese Society for the Promotion of Science (JSPS) ( 17K19668 , 17H05082 , 19K22624 , 20H03665 , 21K18272 to T.S., 21K07084 to K.O., 19K08402 to N.H., 21H02905 to H.O., 20H00536 to T.K., 17H06175 and JP21H05044 to A.Y.), The Japan Agency for Medical Research and Development ( 19ek0109214 to T.S. and CREST - 16813798 , 21gm1510002h0001 to T.K., CREST- 1110009 , CREST JP21gm1110009 , and MOON SHOT JP21zf0127003h to A.Y.), The Yakult Bioscience Research Foundation (T.S.), The Keio University Medical Science Fund (Sakaguchi Memorial, Fukuzawa Memorial) (T.S.), The Takeda Science Foundation , the Mochida Memorial Foundation (T.S.), GSK Science Foundation (T.S.), JSR Research Fund (T.S.), Mitsubishi Foundation (T.K.), and Princess Takamatsu Cancer Research Foundation , Yasuda Medical Foundation (A.Y.). Funding Information: We thank Chiemi Ido, Ena Nomura, Yuzo Koda, Hiroki Kiyohara, Nobuhito Taniki, Koji Okabayashi (Keio University), Daniel Mucida (The Rockefeller University), Mariya London (New York University), Shohei Hori (Tokyo University), Takatoshi Chinen (Kyushu University), and Tsudoi Miyamoto for their discussion and reading of the manuscript and the JKic, Keio core facility for helping with multi-photon microscopy. We thank Melissa Crawford, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. Grants-in-Aid from the Japanese Society for the Promotion of Science (JSPS) (17K19668, 17H05082, 19K22624, 20H03665, 21K18272 to T.S. 21K07084 to K.O. 19K08402 to N.H. 21H02905 to H.O. 20H00536 to T.K. 17H06175 and JP21H05044 to A.Y.), The Japan Agency for Medical Research and Development (19ek0109214 to T.S. and CREST-16813798, 21gm1510002h0001 to T.K. CREST-1110009, CREST JP21gm1110009, and MOON SHOT JP21zf0127003h to A.Y.), The Yakult Bioscience Research Foundation (T.S.), The Keio University Medical Science Fund (Sakaguchi Memorial, Fukuzawa Memorial) (T.S.), The Takeda Science Foundation, the Mochida Memorial Foundation (T.S.), GSK Science Foundation (T.S.), JSR Research Fund (T.S.), Mitsubishi Foundation (T.K.), and Princess Takamatsu Cancer Research Foundation, Yasuda Medical Foundation (A.Y.). Conceptualization: Y.Y. and T.S.; methodology: Y.Y. K.M. T.S. Y.H. S.T. K.O. S.U. K.Y. T.T. T.S. N.S. K.T. K.S. and T.I.; investigation: Y.Y. K.M. T.S. Y.H. and N.S.; visualization: Y.Y. K.M. T.S. Y.H. and N.S.; funding acquisition: T.S. N.H. H.O. A.Y. and T.K.; project administration: T.S.; supervision: T.S. and T.K.; writing – original draft: Y.Y. and T.S.; and writing – review & editing: K.M. Y.Y. Y.M. N.N. A.Y. and T.K. K.M. and T.S. are employees of Miyarisan Pharmaceutical Co. Ltd. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = may,
day = "10",
doi = "10.1016/j.celrep.2022.110773",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}