期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2115230119
关键词
Paneth cell; alpha-defensin; fucosyltransferase 2; IL-22; IL-17a
资金
- University of California San Diego (UCSD) [NINDS NS047101]
- Funds for the Promotion of Joint International Research [18KK0432]
- Institute of Medical Science, the University of Tokyo International Joint Research Project from JSPS [K003]
- Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency [JP15gm0410004h0006]
- Japan Agency forMedical Research and Development (AMED) [JP20gm 1010006h004]
- AMED-the Japan Agency for Medical Research and Development-Science and Technology Research Partnership for Sustainable Development [JP20jm0110012h0006]
- AMED-Practical Research Project for Allergic Diseases and Immunology [JP18ek0410032h0003]
- AMED-Precursory Research for Innovative Medical Care (PRIME) [JP19gm6010005h0004, JP20gm6010012h0004, JP20gm6210024h0001]
- AMED-Science and Technology Platform Program for Advanced Biological Medicine [JP21am0401029h0001]
- AMED-Japan Program for Infectious Diseases Research and Infrastructure [JP20fk0108122h0001]
- AMEDAcceleration Transformative Research for Medical Innovation [JP19im02106 23h0001]
- AMED-the Research Programon Emerging and Re-emerging Infectious Diseases [JP19fk0108 112j0001]
- AMED-Project Focused on Developing Key Technology for Discovering and Manufacturing Drugs for Next-Generation Treatment and Diagnosis
- Center of Innovation Program from Japan Science and Technology Agency
- Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry
- Public/Private R&D Investment Strategic Expansion Program [20AC5004]
- Chiba University-UCSD Center for Mucosal Immunology, Allergy, and Vaccines
- UCSD San Diego Digestive Disease Research Center
- NIH RO1 [AI079145-08]
- 3M Global Giving Donation Fund
- Grant for Joint Research Project of the Institute of Medical Science, the University of Tokyo
- Japanese Society for Immunology-Outstanding Young Women Immunology Researcher Award
- Ministry of Health and Welfare of Japan
- [18H05280]
- [18H02788]
- [26462831]
- [16H06229]
- [16H06243]
- [19K17452]
- [16J06100]
Paneth cells in mice can be differentiated into two subtypes based on their production and utilization of fucosyltransferase 2 (Fut2). Fut2(+) Paneth cells are involved in host defense by creating niches for commensal bacteria and preventing invasion of pathogens.
Paneth cells are intestinal epithelial cells that release antimicrobial peptides, such as alpha-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 a(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 alpha-defensin secretion system via modulation of Fut2 expression, and IL-17a was found to increase the production of alpha-defensin in the intestinal tract. Thus, these intestinal cytokines regulate the development and function of Fut2(+) Paneth cells as part of gut defense.
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