title: Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.
abstract: Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.
authors.affiliation: Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Graduate School of Medicine, Osaka University, 565-0871 Suita, Japan Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, 565-0871 Suita, Japan WPI Immunology Frontier Research Center, Osaka University, 565-0871 Suita, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugawara
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 34141 Daejeon, Republic of Korea.
authors.forename: Min Seong
authors.initials: MS
authors.lastname: Jang
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Jeun
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: Chun-Pyo
authors.initials: CP
authors.lastname: Hong
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Park
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea.
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Hong
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: You-Me
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Ewha Womans University, 158-710 Seoul, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
authors.affiliation: Department of Microbiology, School of Medicine, Gachon University, 21936 Incheon, Republic of Korea.
authors.forename: YunJae
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, 565-0871 Suita, Japan WPI Immunology Frontier Research Center, Osaka University, 565-0871 Suita, Japan MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea jangmh@ibs.re.kr yangbg@ibs.re.kr.
authors.forename: Bo-Gie
authors.initials: BG
authors.lastname: Yang
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, 790-784 Pohang, Republic of Korea WPI Immunology Frontier Research Center, Osaka University, 565-0871 Suita, Japan jangmh@ibs.re.kr yangbg@ibs.re.kr.
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
mesh_terms: D000818:Animals; D010122:Cystinyl Aminopeptidase / Q000235:genetics / Q000276:immunology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: C587672:IL1B protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase