The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens.For these reasons,the intestinal immune system is uniquely dedicated to protect ag...The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens.For these reasons,the intestinal immune system is uniquely dedicated to protect against infections,while avoiding the development of destructive inflammatory responses to the microbiota.Several models have been proposed to explain how the immune system discriminates between,and appropriately responds to,commensal and pathogenic microorganisms.Dendritic cells(DCs)and regulatory T cells(Treg)are instrumental in maintaining immune homeostasis and tolerance in the gut.DCs are virtually omnipresent and are remarkably plastic,having the ability to adapt to the influences of the microenvironment.Different DC populations with partially overlapping phenotypic and functional properties have been described in different anatomical locations.DCs in the draining mesenteric lymph nodes,in the intestinal lamina propria and in Peyer's patches partake both in the control of intestinal inflammation and in the maintenance of gut tolerance.In this respect,gutresident DCs and macrophages exert tolerogenic functions as they regularly encounter and sense commensal bacteria.In contrast,migrating DC subsets that are recruited to the gut as a result of pathogenic insults initiate immune responses.Importantly,tolerogenic DCs act by promoting the differentiation and expansion of Treg cells that efficiently modulate gut inflammation,as shown both in preclinical models of colitis and in patients with inflammatory bowel disease(IBD).This article reviews the phenotypic and functional features of gut DC subsets and discusses the current evidence underpinning the DC contribution to the pathogenesis of the major clinical subtypes of human IBD.It also addresses the potential clinical benefit derived from DC targeting either in vivo or in vitro.展开更多
Irritable bowel syndrome (IBS) is a common gastro-intestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare r...Irritable bowel syndrome (IBS) is a common gastro-intestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome Ⅲ criteria. A combination of the Rome Ⅲ criteria, a physical examination, blood tests, gastros-copy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS:heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following:genetic factors, dietary intake, intestinal flora, or lowgrade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI-and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.展开更多
Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some...Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.展开更多
The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mati...The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.展开更多
Invasive growth of epithelial tumor is a very complex process. Therefore,clarifying the molecular mechanisms of the invasive growth of tumor cells will help us find new targets for cancer therapy,and suppress tumor gr...Invasive growth of epithelial tumor is a very complex process. Therefore,clarifying the molecular mechanisms of the invasive growth of tumor cells will help us find new targets for cancer therapy,and suppress tumor growth and development more effectively.展开更多
基金Supported by The "Stem Cell Project",Fondazione Roma,Italy and by the Associazione Italiana per la Ricerca sul Cancro,Milan,Italy(AIRC,Grant No.8556)
文摘The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens.For these reasons,the intestinal immune system is uniquely dedicated to protect against infections,while avoiding the development of destructive inflammatory responses to the microbiota.Several models have been proposed to explain how the immune system discriminates between,and appropriately responds to,commensal and pathogenic microorganisms.Dendritic cells(DCs)and regulatory T cells(Treg)are instrumental in maintaining immune homeostasis and tolerance in the gut.DCs are virtually omnipresent and are remarkably plastic,having the ability to adapt to the influences of the microenvironment.Different DC populations with partially overlapping phenotypic and functional properties have been described in different anatomical locations.DCs in the draining mesenteric lymph nodes,in the intestinal lamina propria and in Peyer's patches partake both in the control of intestinal inflammation and in the maintenance of gut tolerance.In this respect,gutresident DCs and macrophages exert tolerogenic functions as they regularly encounter and sense commensal bacteria.In contrast,migrating DC subsets that are recruited to the gut as a result of pathogenic insults initiate immune responses.Importantly,tolerogenic DCs act by promoting the differentiation and expansion of Treg cells that efficiently modulate gut inflammation,as shown both in preclinical models of colitis and in patients with inflammatory bowel disease(IBD).This article reviews the phenotypic and functional features of gut DC subsets and discusses the current evidence underpinning the DC contribution to the pathogenesis of the major clinical subtypes of human IBD.It also addresses the potential clinical benefit derived from DC targeting either in vivo or in vitro.
文摘Irritable bowel syndrome (IBS) is a common gastro-intestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome Ⅲ criteria. A combination of the Rome Ⅲ criteria, a physical examination, blood tests, gastros-copy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS:heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following:genetic factors, dietary intake, intestinal flora, or lowgrade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI-and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.
文摘Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.
基金Supported by Grants From the National Natural Science Foundation of China,No.30770988 and No.30971358
文摘The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.
文摘Invasive growth of epithelial tumor is a very complex process. Therefore,clarifying the molecular mechanisms of the invasive growth of tumor cells will help us find new targets for cancer therapy,and suppress tumor growth and development more effectively.
