Intestinal commensal microbiota and cytokines regulate Fut2+Paneth cells for gut defense

Author:

Kamioka Mariko1234ORCID,Goto Yoshiyuki25,Nakamura Kiminori6ORCID,Yokoi Yuki6ORCID,Sugimoto Rina6ORCID,Ohira Shuya6ORCID,Kurashima Yosuke12347,Umemoto Shingo138,Sato Shintaro1910ORCID,Kunisawa Jun24,Takahashi Yu11ORCID,Domino Steven E.12ORCID,Renauld Jean-Christophe13ORCID,Nakae Susumu14,Iwakura Yoichiro15ORCID,Ernst Peter B.3161718,Ayabe Tokiyoshi6ORCID,Kiyono Hiroshi12318ORCID

Affiliation:

1. Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

2. International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

3. Department of Medicine, School of Medicine and Chiba University-University of California San Diego Center for Mucosal Immunology, Allergy and Vaccine (CU-UCSD cMAV), University of California, San Diego, CA 92093

4. Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition, Osaka 567-0085, Japan

5. Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan

6. Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido 001-0021, Japan

7. Department of Innovative Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

8. Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan

9. Mucosal Vaccine Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

10. Department of Immunology and Genomics, Osaka City University, Graduate School of Medicine, Osaka 545-8585, Japan

11. Food Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan

12. Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617

13. Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels B-1200, Belgium

14. Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8528, Japan

15. Center for Experimental Animal Models, Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan

16. Division of Comparative Pathology and Medicine, Department of Pathology, University of California, San Diego, CA 92093

17. Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, CA 92093

18. Future Medicine Education and Research Organization, Chiba University, Chiba 260-8670, Japan

Abstract

SignificancePaneth cells produce granules containing antimicrobial peptides, such as α-defensin for host defense. Examination of the production and utilization of fucosyltransferase 2 (Fut2) by Paneth cells revealed two distinct subsets: Fut2+Paneth cells and Fut2Paneth cells. Compared with Fut2Paneth cells, Fut2+Paneth cells were enriched in granules containing antimicrobial peptides. IL-22 and IL-17a were found to be essential for commensal bacteria-dependent Fut2+Paneth cell development and function as part of gut defense.

Funder

MEXT | Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

the Ministry of Health and Welfare of Japan

NIH

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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