Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy...Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.展开更多
Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cyt...Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.展开更多
Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in geneticall...Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors,which together result in dysregulation of the mucosal immune system.Thus,the majority of previous studies have focused on the immune response within the intestinal wall.The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process,namely the mesenteric fat tissue,the lymphatics and the microvasculature.Broadening our view across the intestinal wall will not only facilitate our understanding of the disease,but will also us to identify future therapeutic targets.展开更多
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
Validating a method of analysis goes through different steps, which aims at testing the normality of measurements distribution, estimating the uncertainty of the components of a measurement （i.e., accuracy and correc...Validating a method of analysis goes through different steps, which aims at testing the normality of measurements distribution, estimating the uncertainty of the components of a measurement （i.e., accuracy and correctness）, and finally, define the control tests of non degradation of the method performances. This paper outlines the steps for validating a biological method of analysis. It involves the construction of an experimental design, a statistical model, and the preparation of an interne laboratory reference material （pilot vaccine）. The latter is used to study the impact of deviation and variation factors, in order to, optimize the analytical method, to evaluate the bias （random error）, and to calculate the uncertainty of measurement, and make the control charts. This method is applied in the titration of live viral vaccines of Gumboro disease on chicken＇s embryos fibroblasts. The experimental results show that potential influence factors related to the titration method had no significant influence on the obtained results. Taking into account these results, an operating mode has been elaborated. The finalized method proved to be faithful to standard deviation of repeatability and reproducibility of 0.21 and 0.22, respectively, with a confidence level of 95%. The calculated uncertainty of measurement is equal to 0.2, which represents the average error level of a titer. A homogeneous stock of interne laboratory reference vaccine （MRIL）, with an average titer of 5.9 log DIT 50, was produced and the control chart set in away to provide the laboratory with an important tool of control and monitoring of the viral titers evolution in time, as well as, the mastery of the validated titration method performances.展开更多
Dear Editor,Infectious bursal disease virus（IBDV）causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwid...Dear Editor,Infectious bursal disease virus（IBDV）causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwide.IBDV replicates mainly in actively dividing B lymphocytes within the bursa of Fabricius（BF）,leading to immunosuppression in affected flocks（Mahgoub et al.,2012）.Viral protein 2（VP2）,展开更多
文摘Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.
文摘Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.
基金Supported by SFB 633 of the Deutsche Forschungsgemeinschaft
文摘Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors,which together result in dysregulation of the mucosal immune system.Thus,the majority of previous studies have focused on the immune response within the intestinal wall.The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process,namely the mesenteric fat tissue,the lymphatics and the microvasculature.Broadening our view across the intestinal wall will not only facilitate our understanding of the disease,but will also us to identify future therapeutic targets.
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Validating a method of analysis goes through different steps, which aims at testing the normality of measurements distribution, estimating the uncertainty of the components of a measurement （i.e., accuracy and correctness）, and finally, define the control tests of non degradation of the method performances. This paper outlines the steps for validating a biological method of analysis. It involves the construction of an experimental design, a statistical model, and the preparation of an interne laboratory reference material （pilot vaccine）. The latter is used to study the impact of deviation and variation factors, in order to, optimize the analytical method, to evaluate the bias （random error）, and to calculate the uncertainty of measurement, and make the control charts. This method is applied in the titration of live viral vaccines of Gumboro disease on chicken＇s embryos fibroblasts. The experimental results show that potential influence factors related to the titration method had no significant influence on the obtained results. Taking into account these results, an operating mode has been elaborated. The finalized method proved to be faithful to standard deviation of repeatability and reproducibility of 0.21 and 0.22, respectively, with a confidence level of 95%. The calculated uncertainty of measurement is equal to 0.2, which represents the average error level of a titer. A homogeneous stock of interne laboratory reference vaccine （MRIL）, with an average titer of 5.9 log DIT 50, was produced and the control chart set in away to provide the laboratory with an important tool of control and monitoring of the viral titers evolution in time, as well as, the mastery of the validated titration method performances.
基金supported by grants AERG 232141/PNBIO 1131032 from the Instituto Nacional de Tecnología Agropecuaria(INTA)PICT 2008-0400 from the Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT),Argentina
文摘Dear Editor,Infectious bursal disease virus（IBDV）causes infectious bursal disease,a highly contagious immunosuppressive disease that affects young chickens and causes economic losses in the poultry industry worldwide.IBDV replicates mainly in actively dividing B lymphocytes within the bursa of Fabricius（BF）,leading to immunosuppression in affected flocks（Mahgoub et al.,2012）.Viral protein 2（VP2）,
