期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：3
DOI：10.1073/pnas.2115230119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Paneth 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 Fut2
− Paneth cells. Compared with Fut2
− Paneth 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.
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.
