Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually inc...Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.展开更多
Helicobacter pylori(H.pylori)is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide.However,its prevalence varies among different geographic areas,and is influenced by several factor...Helicobacter pylori(H.pylori)is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide.However,its prevalence varies among different geographic areas,and is influenced by several factors.The infection can be acquired by means of oral-oral or fecal-oral transmission,and the pathogen possesses various mechanisms that improve its capacity of mobility,adherence and manipulation of the gastric microenvironment,making possible the colonization of an organ with a highly acidic lumen.In addition,H.pylori presents a large variety of virulence factors that improve its pathogenicity,of which we highlight cytotoxin associated antigen A,vacuolating cytotoxin,duodenal ulcer promoting gene A protein,outer inflammatory protein and gamma-glutamyl transpeptidase.The host immune system,mainly by means of a Th1-polarized response,also plays a crucial role in the infection course.Although most H.pylori-positive individuals remain asymptomatic,the infection predisposes the development of various clinical conditions as peptic ulcers,gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas.Invasive and non-invasive diagnostic methods,each of them with their related advantages and limitations,have been applied in H.pylori detection.Moreover,bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection,and new therapy alternatives are being tested to improve H.pylori eradication.Last but not least,the development of effective vaccines against H.pylori infection have been the aim of several research studies.展开更多
AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or d...AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.展开更多
Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained ...Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.展开更多
Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immuno...Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.展开更多
To explore the effect of early enteral nutrition （EN） on postoperative nutritional status, intestinal permeability, and immune 6anction in elderly patients with esophageal cancer or cardiac cancer. Methods： A total...To explore the effect of early enteral nutrition （EN） on postoperative nutritional status, intestinal permeability, and immune 6anction in elderly patients with esophageal cancer or cardiac cancer. Methods： A total of 96 patients with esophageal cancer or cardiac cancer who underwent surgical treatment in our hospital from June 2007 to December 2010 were enrolled in this study. They were divided into EN group （n=50） and parenteral nutrition （PN） group （n=46） based on the nutrition support modes. The body weight, time to first flatus/defecation, average hospital stay, complications and mortality after the surgery as well as the liver function indicators were recorded and analyzed. Peripheral blood samples were collected on the days 1, 4 and 7 after surgery. The plasma diamine oxidase （DAO） activity and D-lactate level were determined to assess the intestinal permeability. The plasma endotoxin levels were determined using dynamic turbidimetric assay to assess the protective effect of EN on intestinal mucosal barrier. The postoperative blood levels of inflammatory cytokines and immunoglobulins were determined using enzyme- linked immunosorbent assay （ELISA）. Results： After the surgery, the time to first flatus/defecation, average hospital stay, and complications were significantly less in the EN group than those in the PN group （P〈0.05）, whereas the EN group had significantly higher albumin levels than the PN group （P〈0.05）. On the 7th postoperative day, the DAO activity, D-lactate level and endotoxin contents were significantly lower in the EN group than those in the PN group （all P〈0.05）. In addition, the EN group had significantly higher IgA, IgG, IgM, and CD4 levels than the PN group （P〈0.05） but significantly lower IL-2, IL-6, and TNF-a levels （P〈0.05）. Conclusions： In elderly patients with esophageal cancer or cardiac cancer, early EN after surgery can effectively improve the nutritional status, protect intestinal mucosal barrier （by reducing plasma展开更多
基金Supported by Grants from the National Natural Science Foundation of China,No.81270477
文摘Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
文摘Helicobacter pylori(H.pylori)is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide.However,its prevalence varies among different geographic areas,and is influenced by several factors.The infection can be acquired by means of oral-oral or fecal-oral transmission,and the pathogen possesses various mechanisms that improve its capacity of mobility,adherence and manipulation of the gastric microenvironment,making possible the colonization of an organ with a highly acidic lumen.In addition,H.pylori presents a large variety of virulence factors that improve its pathogenicity,of which we highlight cytotoxin associated antigen A,vacuolating cytotoxin,duodenal ulcer promoting gene A protein,outer inflammatory protein and gamma-glutamyl transpeptidase.The host immune system,mainly by means of a Th1-polarized response,also plays a crucial role in the infection course.Although most H.pylori-positive individuals remain asymptomatic,the infection predisposes the development of various clinical conditions as peptic ulcers,gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas.Invasive and non-invasive diagnostic methods,each of them with their related advantages and limitations,have been applied in H.pylori detection.Moreover,bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection,and new therapy alternatives are being tested to improve H.pylori eradication.Last but not least,the development of effective vaccines against H.pylori infection have been the aim of several research studies.
基金Supported by Grants from the Key Project of the Eleventh Five-Year Plan of People's Liberation Army,No.06G041
文摘AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.
基金This work was supported by grants from the Beijing Advanced Innovation Center for Genomics at Peking University,Key Technologies R&D Program(2016YFC0900100 and 2016YFC0902300)the National Natural Science Foundation of China(31530036 and 91742203).
文摘Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.
文摘Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.
文摘To explore the effect of early enteral nutrition （EN） on postoperative nutritional status, intestinal permeability, and immune 6anction in elderly patients with esophageal cancer or cardiac cancer. Methods： A total of 96 patients with esophageal cancer or cardiac cancer who underwent surgical treatment in our hospital from June 2007 to December 2010 were enrolled in this study. They were divided into EN group （n=50） and parenteral nutrition （PN） group （n=46） based on the nutrition support modes. The body weight, time to first flatus/defecation, average hospital stay, complications and mortality after the surgery as well as the liver function indicators were recorded and analyzed. Peripheral blood samples were collected on the days 1, 4 and 7 after surgery. The plasma diamine oxidase （DAO） activity and D-lactate level were determined to assess the intestinal permeability. The plasma endotoxin levels were determined using dynamic turbidimetric assay to assess the protective effect of EN on intestinal mucosal barrier. The postoperative blood levels of inflammatory cytokines and immunoglobulins were determined using enzyme- linked immunosorbent assay （ELISA）. Results： After the surgery, the time to first flatus/defecation, average hospital stay, and complications were significantly less in the EN group than those in the PN group （P〈0.05）, whereas the EN group had significantly higher albumin levels than the PN group （P〈0.05）. On the 7th postoperative day, the DAO activity, D-lactate level and endotoxin contents were significantly lower in the EN group than those in the PN group （all P〈0.05）. In addition, the EN group had significantly higher IgA, IgG, IgM, and CD4 levels than the PN group （P〈0.05） but significantly lower IL-2, IL-6, and TNF-a levels （P〈0.05）. Conclusions： In elderly patients with esophageal cancer or cardiac cancer, early EN after surgery can effectively improve the nutritional status, protect intestinal mucosal barrier （by reducing plasma
