A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major ...A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major components of this protective system as for example an intact epithelium, the synthesis of various antimicrobial peptides (AMPs) and the formation of the mucus layer. We highlight the crucial importance of their correct functioning for the maintenance of a proper intestinal function and the prevention of dysbiosis and disease. Barrier disturbances including a defective production of AMPs, alterations in thickness or composition of the intestinal mucus layer, alterations of pattern-recognition receptors, defects in the process of autophagy as well as unresolved endoplasmic reticulum stress result in an inadequate host protection and are thought to play a crucial role in the pathogenesis of the inflammatory bowel diseases Crohn’s disease and ulcerative colitis.展开更多
The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides ...The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease(IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis.展开更多
Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border.In order to ...Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border.In order to perform these diverse functions,spatially distinct compartments of epithelial differentiation are found along the crypt-villus axis,including Paneth cells as a highly specialised cell type.Paneth cells locate in crypts and assist undifferentiated columnar cells,called crypt base columnar cells,and rapidly amplifying cells in the regeneration of absorptive and secretory cell types.There is some evidence that Paneth cells are involved in the configuration and function of the stem cell zone as well as intestinal morphogenesis and crypt fission.However,the flow of Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and partially antagonised by Notch.In addition,mature Paneth cells are essential for the production and secretion of antimicrobial peptides including α-defensins/cryptdins.These antimicrobials are physiologically involved in shaping the composition of the microbiome.The autophagy related 16-like 1(ATG16L1) is a genetic risk factor and is involved in the exocytosis pathway of Paneth cells as well as a linker molecule to PPAR signalling and lipid metabolism.There is evidence that injuries of Paneth cells are involved in the etiopathogenesis of different intestinal diseases.The review provides an overview of the key points of Paneth cell activities in intestinal physiology and pathophysiology.展开更多
A healthy intestine plays an important role in the growth and development of farm animals.In small intestine,Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells(ISCs).Al...A healthy intestine plays an important role in the growth and development of farm animals.In small intestine,Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells(ISCs).Although there has been a lot of studies and reviews on human and murine Paneth cells under intestinal homeostasis or disorders,little is known about Paneth cells in farm animals.Most farm animals possess Paneth cells in their small intestine,as identified by various staining methods,and Paneth cells of various livestock species exhibit noticeable differences in cell shape,granule number,and intestinal distribution.Paneth cells in farm animals and their antimicrobial peptides(AMPs)are susceptible to multiple factors such as dietary nutrients and intestinal infection.Thus,the comprehensive understanding of Paneth cells in different livestock species will contribute to the improvement of intestinal health.This review first summarizes the current status of Paneth cells in pig,cattle,sheep,horse,chicken and rabbit,and points out future directions for the investigation of Paneth cells in the reviewed animals.展开更多
In steady state, the intestinal epithelium forms an important part of the gut barrier to defend against luminal bacterial attack. However, the intestinal epithelium is compromised by ionizing irradiation due to its in...In steady state, the intestinal epithelium forms an important part of the gut barrier to defend against luminal bacterial attack. However, the intestinal epithelium is compromised by ionizing irradiation due to its inherent selfrenewing capacity. In this process, small intestinal bacterial overgrowth is a critical event that reciprocally alters the immune milieu. In other words, intestinal bacterial dysbiosis induces inflammation in response to intestinal injuries, thus influencing the repair process of irradiated lesions. In fact, it is accepted that commensal bacteria can generally enhance the host radiation sensitivity. To address the determination of radiation sensitivity, we hypothesize that Paneth cells press a critical "button" because these cells are central to intestinal health and disease by using their peptides, which are responsible for controlling stem cell development in the small intestine and luminal bacterial diversity. Herein,the most important question is whether Paneth cells alter their secretion profiles in the situation of ionizing irradiation. On this basis, the tolerance of Paneth cells to ionizing radiation and related mechanisms by which radiation affects Paneth cell survival and death will be discussed in this review. We hope that the relevant results will be helpful in developing new approaches against radiation enteropathy.展开更多
基金Supported by Robert Bosch Foundation,Stuttgart,Germany
文摘A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major components of this protective system as for example an intact epithelium, the synthesis of various antimicrobial peptides (AMPs) and the formation of the mucus layer. We highlight the crucial importance of their correct functioning for the maintenance of a proper intestinal function and the prevention of dysbiosis and disease. Barrier disturbances including a defective production of AMPs, alterations in thickness or composition of the intestinal mucus layer, alterations of pattern-recognition receptors, defects in the process of autophagy as well as unresolved endoplasmic reticulum stress result in an inadequate host protection and are thought to play a crucial role in the pathogenesis of the inflammatory bowel diseases Crohn’s disease and ulcerative colitis.
文摘The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease(IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis.
文摘Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border.In order to perform these diverse functions,spatially distinct compartments of epithelial differentiation are found along the crypt-villus axis,including Paneth cells as a highly specialised cell type.Paneth cells locate in crypts and assist undifferentiated columnar cells,called crypt base columnar cells,and rapidly amplifying cells in the regeneration of absorptive and secretory cell types.There is some evidence that Paneth cells are involved in the configuration and function of the stem cell zone as well as intestinal morphogenesis and crypt fission.However,the flow of Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and partially antagonised by Notch.In addition,mature Paneth cells are essential for the production and secretion of antimicrobial peptides including α-defensins/cryptdins.These antimicrobials are physiologically involved in shaping the composition of the microbiome.The autophagy related 16-like 1(ATG16L1) is a genetic risk factor and is involved in the exocytosis pathway of Paneth cells as well as a linker molecule to PPAR signalling and lipid metabolism.There is evidence that injuries of Paneth cells are involved in the etiopathogenesis of different intestinal diseases.The review provides an overview of the key points of Paneth cell activities in intestinal physiology and pathophysiology.
基金the Joint Funds of the National Natural Science Foundation of China(U22A20511)China Agriculture Research System(CARS-36)Hubei Provincial Key R&D Program(2021BBA083).
文摘A healthy intestine plays an important role in the growth and development of farm animals.In small intestine,Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells(ISCs).Although there has been a lot of studies and reviews on human and murine Paneth cells under intestinal homeostasis or disorders,little is known about Paneth cells in farm animals.Most farm animals possess Paneth cells in their small intestine,as identified by various staining methods,and Paneth cells of various livestock species exhibit noticeable differences in cell shape,granule number,and intestinal distribution.Paneth cells in farm animals and their antimicrobial peptides(AMPs)are susceptible to multiple factors such as dietary nutrients and intestinal infection.Thus,the comprehensive understanding of Paneth cells in different livestock species will contribute to the improvement of intestinal health.This review first summarizes the current status of Paneth cells in pig,cattle,sheep,horse,chicken and rabbit,and points out future directions for the investigation of Paneth cells in the reviewed animals.
基金National Natural Science Foundation of China,No.81874254 and No.81773353。
文摘In steady state, the intestinal epithelium forms an important part of the gut barrier to defend against luminal bacterial attack. However, the intestinal epithelium is compromised by ionizing irradiation due to its inherent selfrenewing capacity. In this process, small intestinal bacterial overgrowth is a critical event that reciprocally alters the immune milieu. In other words, intestinal bacterial dysbiosis induces inflammation in response to intestinal injuries, thus influencing the repair process of irradiated lesions. In fact, it is accepted that commensal bacteria can generally enhance the host radiation sensitivity. To address the determination of radiation sensitivity, we hypothesize that Paneth cells press a critical "button" because these cells are central to intestinal health and disease by using their peptides, which are responsible for controlling stem cell development in the small intestine and luminal bacterial diversity. Herein,the most important question is whether Paneth cells alter their secretion profiles in the situation of ionizing irradiation. On this basis, the tolerance of Paneth cells to ionizing radiation and related mechanisms by which radiation affects Paneth cell survival and death will be discussed in this review. We hope that the relevant results will be helpful in developing new approaches against radiation enteropathy.
