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Gut virome:New key players in the pathogenesis of inflammatory bowel disease

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World Journal of Methodology 2025年第2期15卷 27-43页

作者： Helal F Hetta Rehab Ahmed Yasmin N Ramadan Hayam Fathy Mohammed Khorshid Mohamed M Mabrouk Mai Hashem Department of Medical Microbiology and immunology Faculty of MedicineAssiut UniversityAssiut 71515Egypt division of Microbiology Immunology and BiotechnologyFaculty of pharmacyUniversity of TabukTabuk 71491Saudi Arabia division of Microbiology Immunology and BiotechnologyDepartment of Natural Products and Alternative MedicineFaculty of PharmacyUniversity of TabukTabuk 71491Saudi Arabia Department of Internal Medicine Division HepatogastroenterologyAssiut UniversityAssiut 71515Egypt Department of Clinical Research Egyptian Developers of Gastroenterology and Endoscopy FoundationCairo 11936Egypt Department of Internal Medicine Faculty of Medicine.Tanta UniversityTanta 31527Egypt Department of Tropical Medicine Gastroenterology and HepatologyAssiut University HospitalAssiut 71515Egypt

Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the *** the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major *** gut virome is a group of viruses found in great frequency in the gastrointestinal tract of *** gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and *** majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the *** conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.

关键词： Inflammatory bowel disease Pathogenesis Gut virome Bacteriophage Eukaryotic viruses

Assembly of IMPDH2-Based,CTPS-Based,and Mixed Rod/Ring Structures Is Dependent on Cell Type and Conditions of Induction

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Journal of Genetics and Genomics 2015年第6期42卷 287-299页

作者： Gerson Dierley Keppeke S.John Calise Edward K.L.Chan Luis Eduardo C.Andrade rheumatology division Federal University of Sao Paulo Department of Oral Biology University of Florida immunology division Fleury Medicine and Health Laboratories

Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR *** La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR *** He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS *** and MPA treatments induced only IMPDH2-based *** were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 *** 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based *** results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.

关键词： Nucleotide synthesis Enzyme aggregation Enzyme inhibition IMPDH2 CTPS

Adaptive immunity in the liver

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Cellular & Molecular immunology 2016年第3期13卷 354-368页

作者： Zongwen Shuai Miranda WY Leung Xiaosong He Weici Zhang Guoxiang Yang Patrick SC Leung M Eric Gershwin division of rheumatology Allergy and Clinical Immunology University of California Davis School of Medicine Davis CA 95616 USA Department of rheumatology and immunology The First Affiliated Hospital of Anhui Medical University Hefei 230022 China.

The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver.

关键词： adaptive immunity T cells immunopathogenesis antiviral immunity

Proteomic analysis reveals distinctive protein profiles involved in CD8^(+) T cell-mediated murine autoimmune cholangitis

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Cellular & Molecular immunology 2018年第8期15卷 756-767页

作者： Weici Zhang Ren Zhang Jun Zhang Ying Sun Patrick SC Leung Guo-Xiang Yang Zongwen Shuai William M Ridgway M Eric Gershwin division of rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavisCaliforniaUSA Department of Pathogenic Biology and immunology Guangzhou University of Chinese MedicineGuangzhou 510006China Center for non-infectious liver diseases Beijing 302 HospitalBeijing 100039China Department of rheumatology and immunology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China division of immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267

Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver,and T cells are critical drivers in this ***,little is known about the regulation of their functional behavior during disease *** previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type Ⅱ(dnTGFβ RII)spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis(PBC).Adoptive transfer of CD8^(+) but not CD4^(+) T cells into Rag1^(−/−)mice reproduced the disease,demonstrating a critical role for CD8^(+) T cells in PBC ***,we used SOMAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different *** addition,we analyzed CD8 protein profiles after adoptive transfer of splenic CD8^(+) cells into Rag1^(−/−)*** use of the unique SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells,which are key to biliary *** total,254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8^(+) cells compared to donor splenic CD8^(+) *** contrast to donor splenic CD8^(+) cells,recipient hepatic CD8^(+) cells expressed distinct profiles for proteins involved in chemokine signaling,focal adhesion,T cell receptor and natural killer cell-mediated cytotoxicity pathways.

关键词： autoimmune cholangitis CD8 dnTGFβRII mice proteomic analysis

Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

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Cellular & Molecular immunology 2021年第3期18卷 764-766页

作者： Konstantin Kotschenreuther Iris Waque Shuaifeng Yan Anja Meyer Thom Haak Julia von Tresckow Joanna Schiller Lydia Gloyer Mara Dittrich-Salamon David M.Kofler Laboratory of Molecular immunology and division of Clinical immunology and rheumatology University of CologneCologneGermany DepartmentⅠof Internal Medicine University of CologneCologneGermany

The legalization of cannabinoids for medical use has reinforced their emerging role as a treatment of chronic pain in patients with cancer or rheumatic diseases.1,2 In addition to their role as pain relievers,evidence obtained from animal models suggests that cannabinoids have immunosuppressive properties.3 However,a definite immunosuppressive function of cannabinoids has not yet been confirmed in clinical trials.

关键词： rheumatic Th17 patients

Neuroprotective role of galectin-1 in central nervous system pathophysiology

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Neural Regeneration Research 2016年第6期11卷 896-897页

作者： Ravikumar Aalinkeel Supriya D.Mahajan Department of Medicine Division of Allergy Immunology and Rheumatology State University of New York at Buffalo Clinical Translational Research Center

Galectins are a family of endogenousβglycan-binding proteins that play an important role in the modulation of inflammationassociated with neurodegeneration as seen in various neurological disorders such as dementia,m... 详细信息

关键词： galectin glycan neurological microglia endogenous infiltrating specifically neuronal pathology homeostasis

Failure of a T cell regulator: CD6 contributes to the aggravation of autoimmune inflammation

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Cellular & Molecular immunology 2019年第9期16卷 733-734页

作者： Anja Meyer David M.Kofler division of Clinical immunology and rheumatology Department I of Internal MedicineUniversity of CologneCologne 50937Germany

The scavenger-like lymphocyte receptor CD6 is a regulator of T cell functions,and is associated with autoimmune ***,the specific contribution of CD6 to autoimmunity remains *** physiological conditions,CD6 associates with the T cell antigen receptor(TCR)/CD3 complex at the center of the immunological synapse and regulates T cell responses through activation-dependent recruitment of the positive regulator SLP-76 and other downstream signaling effectors.1,2 In recent years,immune-activating and immune-inhibiting functions of CD6 have been reported,indicating a dual role of CD6 in T cell activation.1 It has been postulated that the strength of TCR activation determines whether CD6 enhances or inhibits TCR signaling.1 This possible counter-regulatory role of CD6 may contribute to the control of T cell responses.

关键词： autoimmune inflammation CD6

MicroRNA in TLR signaling and endotoxin tolerance

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Cellular & Molecular immunology 2011年第5期8卷 388-403页

作者： Md A Nahid Minoru Satoh Edward KL Chan Department of Oral Biology University of FloridaGainesvilleFLUSA division of rheumatology and Clinical immunology Department of Medicineand PathologyImmunologyand Laboratory MedicineUniversity of FloridaGainesvilleFLUSA

Toll-like receptors(TLRs)in innate immune cells are the prime cellular sensors for microbial *** activation leads to the production of proinflammatory mediators and thus TLR signaling must be properly regulated by various mechanisms to maintain ***4-ligand lipopolysaccharide(LPS)-induced tolerance or cross-tolerance is one such mechanism,and it plays an important role in innate *** is established and sustained by the activity of the microRNA miR-146a,which is known to target key elements of the myeloid differentiation factor 88(MyD88)signaling pathway,including IL-1 receptor-associated kinase(IRAK1),IRAK2 and tumor-necrosis factor(TNF)receptor-associated factor 6(TRAF6).In this review,we comprehensively examine the TLR signaling involved in innate immunity,with special focus on LPS-induced *** function of TLR ligand-induced microRNAs,including miR-146a,miR-155 and miR-132,in regulating inflammatory mediators,and their impact on the immune system and human diseases,are *** of these microRNAs may affect TLR pathway activation and help to develop therapeutics against inflammatory diseases.

关键词： innate immunity lipopolysaccharide LPS tolerance microRNA Toll-like receptor

Juvenile dermatomyositis:advances in clinical presentation,myositis-specific antibodies and treatment

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World Journal of Pediatrics 2020年第1期16卷 31-43页

作者： Jian-Qiang Wu Mei-Ping Lu Ann M.Reed Department of rheumatology immunology and Allergy Children's HospitalZhejiang University School of MedicineHangzhou 310052China Department of Pediatrics Division of Pediatric RheumatologyDuke University School of MedicineDurham 27710USA

Background Juvenile dermatomyositis(JDM)is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin,muscle and vital *** the clinical features and treatment of JDM have not been fully *** sources Databases underwent through PubMed for articles about the clinical features,myositis-specific antibodiesof JDM and its treatment,and we selected publications written in English which were relevant to the topic of this *** Clinical features and myositis-specific antibodies may predict the severity and prognosis of *** the mortality rate has been lower with traditional treatments,such as corticosteroid,intravenous immunoglobulin,and diseasemodifying anti-rheumatic drugs such as methotrexate,their usages are *** biological therapies seem to be effective for refractory JDM patients,but more clinical trials are *** JDM is a sever disease of *** need to better understand recent advances of JDM in the context of clinical features including skin manifestations,muscle weakness and organ damage,myositis-specific antibodies and their associated outcomes and the treatment of disease.

关键词： Biologic agents Extramuscular manifestations Juvenile dermatomyositis Myositis autoantibodies