International Research and Development Center for …in the mucosal surface including gastrointestinal tract. However, C. albicans also have been reported to exert pathogenic effects

1. nnate lymphoid cells govern intestinal epi-thelial a1 2-fucosylation

Yoshiyuki Goto1,2, Satoshi Uematsu2,3,4, and HiroshiKiyono1,5－7: 1International Research and Develop-ment Center for Mucosal Vaccine, Institute forMedical Science, The University of Tokyo, 2Divi-sion of Molecular Immunology, Medical MycologyResearch Center, Chiba University, 3Division ofInnate immune regulation, 4Department of Mu-cosal Immunology, School of Medicine, Chiba Uni-versity, 5Mucosal Immunology and Allergy Thera-peutics, Institute for Global Prominent Research,Chiba University, 6Division of Gastroenterology,Department of Medicine, School of Medicine, CU-UCSD Center for Mucosal Immunology, Allergyand Vaccines, University of California, San Diego,7Division of Mucosal Immunology, IMSUT Distin-guished Professor Unit, The Institute of MedicalScience, The University of Tokyo.

a1, 2-fucosyl linkages located to terminal carbo-hydrate moiety expressed on intestinal epithelialcells is catalyzed by fucosyltransferase 2 (Fut2). Epi-thelial a1, 2-fucose is one of symbiotic factorswhich mediate host-microbiota interaction. For ex-ample, epithelial a1, 2-fucose is utilized as a dietary

carbohydrate by various symbiotic bacteria such asBacteroides. Therefore, disruption of Fut2 leads todysbiosis both in mice and human and predisposedto the development of inflammatory diseases suchas Crohn's disease. Despite of the importance forintestinal and systemic homeostasis, the molecularand cellular mechanisms of the induction of epithe-lial Fut2 and subsequent a1, 2-fucosylation remainunknown. We found that group 3 innate lymphoidcells (ILC3) are critical inducers of intestinal epithe-lial Fut2 expression and fucosylation that is medi-ated by the production of interleukin 22 and lym-photoxin from ILC3 in a commensal bacteria-de-pendent and -independent manner, respectively.Fut2-deificient mice are susceptible to the infectionby pathogenic microorganisms. These data unveil anovel function of ILC3 in creating the appropriatesymbiotic environment and protective platformagainst pathogenic microorganisms through regu-lating the epithelial a1, 2-fucosylation.

2. Pathogenic fungi induce epithelial a1 2-fuco-sylation in the gut

Yoshiyuki Goto1,2 , Miho Uematsu1 , TetsuroMatano1: 1Division of Mucosal symbiosis, Interna-tional Research and Development Center for Mu-

International Research and Development Center for Mucosal Vaccines

Division of Mucosal Symbiosis粘膜共生学分野

n ite Professor Tetsuro Matano, M.D., D.M.Sc.Project Associate Professor oshiyuki oto, Ph.D.Project Assistant Professor Miho e atsu, Ph.D.

委嘱教授 博士（医学） 俣 野 哲 朗特任准教授 博士（医学） 後 藤 義 幸特任助教 博士（医学） 植 松 未 帆

Gastrointestinal tract is a unique organ which is constitutively exposed by variousantigens including commensal microbiota. In order to create symbiotic environ-ment to non-pathogenic luminal microorganisms, epithelial cells (ECs) and im-mune cells cooperatively establish homeostasis of intestinal microenvironment.We aim to identify the mechanisms of epithelial a1, 2-fucosylation, one of symbi-otic factors between host and microbiota, and uncover the role of ECs-immunecell network in the establishment of intestinal homeostasis.

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cosal Vaccine, Institute for Medical Science, TheUniversity of Tokyo, 2Division of Molecular Immu-nology, Medical Mycology Research Center, ChibaUniversity.

Intestinal epithelial cells are first line of defenseagainst infection by pathogenic microorganisms.Candida albicans are one of commensal fungi residein the mucosal surface including gastrointestinaltract. However, C. albicans also have been reportedto exert pathogenic effects in the immunocom-promised host and expand to the systemic co-mopartments, which is called invasive candidasis.Invasive candidiasis triggered by C. albicans trig-

gered by colonization in the gut is one of the seri-ous infectious disease in the world. So far, it is un-clear how C. albicans colonize and affect epithelialphysiology in the gut. To investigate this, we estab-lished C. albicans colonizing model by using severalantibiotics treated mice and found that C. albicanscolonization induce epithelial a1, 2-fucosylation inthe gut. Because epithelial a1, 2-fucose is one ofsymbiotic factor between host and commensal bac-teria, this data suggests that C. albicans affect epi-thelial glycosylation and host epithelial cells mayprotect C. albicans infection by modulating com-mensal microbiota.

Publications

日本語総説1. 後藤義幸．自然リンパ球による腸管上皮細胞の糖鎖修飾誘導システム．医歯薬出版．医学のあゆみ．２６５（１３），１１５５―１１５８，２０１８

2. 白 旭，畢 蓓蓓，後藤義幸．腸内細菌叢が代謝・免疫に与える基本的理解．最新医学社．最新医学．７３（４），５０４―５０８，２０１８

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