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AIm associated with the Igm pentamer: attackers on stand-by at aircraft carrier

Cellular & molecular Immunology 2018年第6期15卷 563-574页

作者： Toru miyazaki Tomoko Yamazaki Ryoichi Sugisawa m eric gershwin Satoko Arai Laboratory of molecular Biomedicine for Pathogenesis Center for Disease Biology and Integrative MedicineFaculty of MedicineThe University of TokyoTokyo 113-0033Japan CREST Japan Agency for Medical Research and DevelopmentTokyo 113-0033Japan max Planck-The University of Tokyo Center for Integrative Inflammology Tokyo 113-0033Japan Division of Rheumatology Allergy and Clinical Immunology The University of California School of MedicineDavisCA 95616USA

Circulating immunoglobulin m(Igm)exists in a pentameric form,possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens;thus,it is involved in both beneficial and detrimental immune responses,including protection from infection and the progression of *** the other hand,Igm also behaves as a carrier of the apoptosis inhibitor of macrophage(AIm)protein,storing a large amount of the inactivated form of AIm in the blood through this *** different disease conditions,AIm can dissociate from Igm locally or systemically to exert its function,inducing the removal of various biological debris such as excess fat,bacteria,cancer cells or dead cell *** typically,upon induction of acute kidney injury(AKI),Igm-free AIm is filtered by the glomerulus in the kidney,which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules,thereby facilitating the repair of kidney ***,cats exhibit a deficiency in AIm release from Igm,which may increase their susceptibility to renal ***,association with AIm inhibits Igm binding to the Fcα/μreceptor on follicular dendritic cells at the splenic germinal center,thereby protecting the Igm immune complex from Fcα/μreceptor-mediated internalization,which supports Igm-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody *** regulation of AIm–Igm binding,resulting from the discovery of reciprocal actions between AIm and Igm,could lead to the development of novel therapies against different diseases.

关键词： apoptosis inhibitor of macrophage(AIm) immunoglobulin m(Igm) acute kidney injury(AKI) hepatocellular carcinoma(HCC) cat renal failure

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The long and latent road to autoimmunity

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Cellular & molecular Immunology 2018年第6期15卷 543-546页

作者： Carlo Selmi Bin Gao m.eric gershwin Division of Rheumatology and Clinical Immunology Humanitas Research HospitalRozzanoMilanItaly Department BIOmETRA University of MilanMilanItaly Laboratory of Liver Diseases National Institute for Alcohol Abuse and AlcoholismNational Institutes of HealthBethesdaMDUSA Division of Rheumatology Allergyand Clinical ImmunologyUniversity of CaliforniaDavisCAUSA

Autoimmune diseases affect nearly 5%of the general population,yet etiology remains poorly *** factors are clearly necessary but remain insufficient to explain the loss of tolerance;environmental and stochastic factors fill this *** paradigm is indicated by the concordance rates(ranging between 4 and 63%)for autoimmune diseases among monozygotic twins,who share an identical genome,compared to the invariably lower rates in dizygotic *** term“exposome”cumulatively refers to the non-hereditary(i.e.,environmental)factors that account for the remaining susceptibility and include endogenous factors such as *** evidence suggests that exposure to infections,drugs,vaccines,and chemicals may contribute to the loss of *** mechanisms by which environmental factors can shape the immune system to generate autoimmunity include molecular mimicry,self-antigen modification,bystander activation,and immune reactivity *** all cases,we should first consider the prolonged time between an environmental trigger and the appearance of autoreactivity and subsequent clinical *** this special issue,several excellent reviews discuss the potential mechanisms linking environmental factors and autoimmunity.

关键词： endogenous latent reactivity

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Long noncoding RNA lncKdm2b: A critical player in the maintenance of group 3 innate lymphoid cells

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Cellular & molecular Immunology 2018年第1期15卷 5-7页

作者： Can-Jie Guo Weici Zhang m eric gershwin Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease Shanghai Institute of Digestive Disease Shanghai200001China Division of Rheumatology Allergy and Clinical ImmunologySchool of MedicineUniversity of CaliforniaDavis95616CAUSA

Innate lymphoid cells(ILCs)represent a heterogeneous population,including both effectors and regulators of innate immunity,inflammation and tissue modeling.1 ILCs are categorized into three subgroups,ILC1s,ILC2s and ILC3s,based on similarities in phenotypic,ontogenetic and functional characteristics.2 ILC3s intrinsically require the transcription factor retinoic acid receptor-related orphan receptorγt(RORγt)for their development and function.3 In response to specific stimuli,ILC3s produce IL-17 and IL-22 and play a critical role in intestinal mucosal protection,inflammation and innate responses 4 accompanied by a series of pathophysiological changes involving large-scale genetic upregulation and downregulation.5,6 However,a key challenge remains in understanding the molecular mechanisms underlying the development and maintenance of ILC3s.

关键词： lymphoid inflammation immunity

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Exosomal microRNA in autoimmunity

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Cellular & molecular Immunology 2019年第12期16卷 932-934页

作者： Weijia Duan Weici Zhang Jidong Jia Qianjin Lu m.eric gershwin Beijing Key Laboratory of Translational medicine on Cirrhosis Liver Research CenterNational Clinical Research Center for Digestive DiseasesBeijing Friendship HospitalCapital Medical University100050 BeijingChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavisCA 95616USA Department of Dermatology Second Xiangya HospitalHunan Key Laboratory of Medical EpigenomicsCentral South UniversityChangsha 410011 HunanChina

Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a critical role in intercellular *** exosomal miRNA profile reflects the cellular pathophysiological status and modulates multiple biological *** evidence indicates that exosomes and miRNAs are biomarkers for disease diagnosis and may have therapeutic *** studies on exosomal miRNAs have brought new insights into understanding autoimmune *** article summarizes the detection methodologies and updates the potential applications of exosomal miRNAs in autoimmune diseases.

关键词： somal diagnosis autoimmune

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Primary biliary cholangitis: personalized medicine for optimal therapeutic opportunities

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Science Bulletin 2022年第24期67卷 2498-2501页

作者： Yulong Shang Patrick S.C.Leung m.eric gershwin Ying Han National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases Xijing HospitalAir Force Military Medical UniversityXi’an 710032China Division of Rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavis 95616USA

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is characterized by inflammation of the interlobular bile ducts. Although PBC is a slowly progressive disease, with a natural history of 10–15 years leading to end-stage liver disease, highrisk cases may rapidly progress to decompensated cirrhosis or even death. As the most common autoimmune liver disease, the prevalence of PBC has been increasing globally, largely due to increased disease awareness, improved diagnosis, and treatment with ursodeoxycholic acid (UDCA). PBC is more likely to occur in middle-aged women, with a female-to-male ratio ranging from 1.6 to10;however, men have a higher disease severity [1,2].

关键词： diagnosis inflammation Primary

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Novel trends in celiac disease

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Cellular & molecular Immunology 2011年第2期8卷 121-125页

作者： Torsten matthias Sandra Neidhofer Sascha Pfeiffer Kai Prager Sandra Reuter m eric gershwin AESKU.KIPP Institute WendelsheimGermany AESKU.Diagnostics GmbH&Co.KG WendelsheimGermany Division of Rheumatology Allergyand Clinical ImmunologyUniversity of CaliforniaDavisCAUSA

Celiac disease(CD)is one of the most common food intolerances in developed *** affects genetically susceptible individuals and has severe consequences if it remains undiagnosed.A disease known for more than a century,it is still the focus for experts from various fields of research and ***,pathologists,immunologists,food engineers and dieticians share their knowledge and expertise to improve the conditions of CD *** new insights in the pathomechanism of gluten processing and antigen presentation in CD,it was possible to improve the diagnostic antigen mimicking the primary epitope in *** celiac neo-epitopes are comprised of a complex of gliadin peptides crosslinked with transglutaminase(tTg).They are an early diagnostic marker for CD which occurs up to 6 months earlier than classical markers known to miss a certain amount of CD patients.

关键词： celiac disease tissue transglutaminase celiac neo-epitope gluten diagnostic marker

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Etiopathogenesis of primary biliary cirrhosis

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World Journal of Gastroenterology 2008年第21期14卷 3328-3337页

作者： Ana Lleo Pietro Invernizzi Ian R mackay Harry Prince Ren-Qian Zhong m eric gershwin Division of Internal medicine and Liver Unit San Paolo Hospital School of Medicine University of Milan Milan 20142 Italy Division of Rheumatology Allergy and Clinical Immunology University of California at Davis Davis CA 95616 United States Department of Biochemistry & molecular Biology Monash University Clayton Victoria 3800 Australia Focus Diagnostics 5785 Corporate Avenue Cypress CA 90630 United States Laboratory Diagnostics of Changzheng Hospital Second Military Medical University and Clinical Immunology Center of PLA Shanghai 200003 China

Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver *** serological hallmark of the disease is the presence of circulating antimitochondrial antibodies(AmA).These reflect the presence of autoreactive T and B cells to the culprit antigens,the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes,chiefly pyruvate dehydrogenase(PDC-E2).The disease results from a combination of genetic and environmental risk *** predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic *** triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical *** mimetopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or,alternatively,environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic.A further alternative as a source of antigen is PDC-E2 derived from apoptotic *** the effector phase the biliary ductular cell,by reason of itsproclivity to express the antigen PDC-E2 in the course of apoptosis,undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and *** this article,we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data,new developments and theories,and nominate directions for future research.

关键词： Autoantibodies Autoreactive T cells 2-oxoacid dehydrogenase Biliary epithelial cells Primary biliary cirrhosis

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Experimental evidence on the immunopathogenesis of primary biliary cirrhosis

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Cellular & molecular Immunology 2010年第1期7卷 1-10页

作者： Carlo Selmi Francesca meda Anaid Kasangian Pietro Invernizzi Zhigang Tian Zhexiong Lian mauro Podda m eric gershwin Department of Translational medicine Universitàdegli Studi di MilanoMilanItaly Department of medicine IRCCS Istituto Clinico Humanitas RozzanoMilanItaly Divisionof Rheumatology Allergyand Clinical ImmunologyUniversity of California at DavisDavisCAUSA Institute of Immunology University of Science and Technology of ChinaHefeiChina

Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease for which an autoimmune pathogenesis is supported by clinical and experimental data,including the presence of autoantibodies and autoreactive T *** etiology remains to be determined,yet data suggest that both a susceptible genetic background and unknown environmental factors determine disease *** infectious and chemical candidates have been proposed to trigger the disease in a genetically susceptible host,mostly by molecular *** recently,several murine models have been reported,including genetically determined models as well as models induced by immunization with xenobiotics and bacteria.

关键词： pathogenesis cirrhosis biliary

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Handbook of Nutrition and Immunity 1

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2004年

作者： m. eric gershwin Penelope Nestel Carl L. Keen

ISBN: (数字)9781592597901

ISBN: (纸本)9781588293084;9781468498646

Because nutrient deficiencies can alter immune response to produce a higher incidence of infection and increased mortality-especially in children-it is important in clinical practice, both as a therapeutic and preventive measure, to determine whether the patient is malnourished. In Handbook of Nutrition and Immunity, an international panel of physicians, pediatricians, immunologists, and public health nutritionists concisely review for front-line health care providers and researchers the practical aspects related to evaluating nutrition and immunology in the field. Here the busy physician and investigator will quickly find a clear and up-to-date understanding of the essential immunological facts in adult and child nutrition. Citing the latest research findings, the authors explain the role of nutrition in such current health issues as HIV, malaria, food allergies, diarrhea, and acute respiratory infections, and review the impact of macro- and micronutrient deficiencies, dietary fat, and antioxidants on immune status. They also discuss the evaluation of immune function in the nutritionally at-risk patient, the immunological effects of severe undernutrition in children, the assessment of nutrition in the field with and without sophisticated facilities, and the special case of the pregnant and lactating woman. As an added value, a compact disk accompanies the book for downloading an ebook version to the reader's PC or PDA.;Comprehensive and holistic, the Handbook of Nutrition and Immunity illuminates for busy health care providers and scientists the interaction and linkages between nutrition and immunology and provides an up-to-date understanding of the practical problems associated with evaluating nutritional and immune status in the field.

关键词： Public Health Immunology Nutrition

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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

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