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
Crohn’s disease(CD)is a chronic inflammatory bowel disease.Research has identified genetic predisposition and environmental factors as key elements in the development of the disease.However,the precise mechanism that...Crohn’s disease(CD)is a chronic inflammatory bowel disease.Research has identified genetic predisposition and environmental factors as key elements in the development of the disease.However,the precise mechanism that initiates immune activation remains undefined.One pathway for luminal antigenic molecules to enter the sterile lamina propria and activate an immune response is via transcytosis.Transcytosis,although tightly regulated by the cell,has the potential for transepithelial transport of bacteria and highly antigenic luminal molecules whose uncontrolled translocation into the lamina propria can be the source of immune activation.Viewed as a whole,the evidence suggests that unregulated intestinal epithelial transcytosis is involved in the inappropriate presentation of immunogenic luminal macromolecules to the intestinal lamina propria.Thus fulfilling the role of an early pre-morbid mechanism that can result in antigenic overload of the lamina propria and initiate an immune response culminating in chronic inflammation characteristic of this disease.It is the aim of this paper to present evidence implicating enterocyte transcytosis in the early etio-pathogenesis of CD.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Crohn’s disease(CD)is a chronic inflammatory bowel disease.Research has identified genetic predisposition and environmental factors as key elements in the development of the disease.However,the precise mechanism that initiates immune activation remains undefined.One pathway for luminal antigenic molecules to enter the sterile lamina propria and activate an immune response is via transcytosis.Transcytosis,although tightly regulated by the cell,has the potential for transepithelial transport of bacteria and highly antigenic luminal molecules whose uncontrolled translocation into the lamina propria can be the source of immune activation.Viewed as a whole,the evidence suggests that unregulated intestinal epithelial transcytosis is involved in the inappropriate presentation of immunogenic luminal macromolecules to the intestinal lamina propria.Thus fulfilling the role of an early pre-morbid mechanism that can result in antigenic overload of the lamina propria and initiate an immune response culminating in chronic inflammation characteristic of this disease.It is the aim of this paper to present evidence implicating enterocyte transcytosis in the early etio-pathogenesis of CD.
