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

Autor: Kamioka M; Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; 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.; 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., Goto Y; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan., Nakamura K; Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido 001-0021, Japan., Yokoi Y; Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido 001-0021, Japan., Sugimoto R; Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido 001-0021, Japan., Ohira S; Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido 001-0021, Japan., Kurashima Y; Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; 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.; 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.; Department of Innovative Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan., Umemoto S; Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; 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.; Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan., Sato S; Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; Mucosal Vaccine Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.; Department of Immunology and Genomics, Osaka City University, Graduate School of Medicine, Osaka 545-8585, Japan., Kunisawa J; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; 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., Takahashi Y; Food Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan., Domino SE; Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617., Renauld JC; Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels B-1200, Belgium., Nakae S; Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8528, Japan., Iwakura Y; Center for Experimental Animal Models, Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan., Ernst PB; 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.; Division of Comparative Pathology and Medicine, Department of Pathology, University of California, San Diego, CA 92093.; Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, CA 92093.; Future Medicine Education and Research Organization, Chiba University, Chiba 260-8670, Japan., Ayabe T; Department of Cell Biological Science, Graduate School of Life Science, Faculty of Advanced Life Science, Hokkaido University, Hokkaido 001-0021, Japan., Kiyono H; Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; kiyono@ims.u-tokyo.ac.jp.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.; 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.; Future Medicine Education and Research Organization, Chiba University, Chiba 260-8670, Japan.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Jan 18; Vol. 119 (3).
DOI: 10.1073/pnas.2115230119
Abstrakt: Paneth cells are intestinal epithelial cells that release antimicrobial peptides, such as α-defensin as part of host defense. Together with mesenchymal cells, Paneth cells provide niche factors for epithelial stem cell homeostasis. Here, we report two subtypes of murine Paneth cells, differentiated by their production and utilization of fucosyltransferase 2 (Fut2), which regulates α(1,2)fucosylation to create cohabitation niches for commensal bacteria and prevent invasion of the intestine by pathogenic bacteria. The majority of Fut2 - Paneth cells were localized in the duodenum, whereas the majority of Fut2 + Paneth cells were in the ileum. Fut2 + Paneth cells showed higher granularity and structural complexity than did Fut2 - Paneth cells, suggesting that Fut2 + Paneth cells are involved in host defense. Signaling by the commensal bacteria, together with interleukin 22 (IL-22), induced the development of Fut2 + Paneth cells. IL-22 was found to affect the α-defensin secretion system via modulation of Fut2 expression, and IL-17a was found to increase the production of α-defensin in the intestinal tract. Thus, these intestinal cytokines regulate the development and function of Fut2 + Paneth cells as part of gut defense.
Competing Interests: The authors declare no competing interest.
(Copyright © 2022 the Author(s). Published by PNAS.)
Databáze: MEDLINE