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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

Guillain–Barré syndrome, transverse myelitis and infectious diseases

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Cellular & Molecular Immunology 2018年第6期15卷 547-562页

作者： Yhojan Rodríguez Manuel Rojas Yovana Pacheco Yeny Acosta-Ampudia Carolina Ramírez-Santana Diana M Monsalve M eric Gershwin Juan-Manuel Anaya Center for Autoimmune Diseases Research(CREA) School of Medicine and Health SciencesUniversidad del RosarioBogotaColombia Division of Rheumatology Allergy and Clinical ImmunologyUniversity of California DavisSchool of MedicineDavisCAUSA

Guillain–Barrésyndrome(GBS)and transverse myelitis(TM)both represent immunologically mediated polyneuropathies of major clinical *** are thought to have a genetic predisposition,but as of yet no specific genetic risk loci have been clearly *** are considered autoimmune,but again the etiologies remain *** may be induced via molecular mimicry,particularly from infectious agents and vaccines,but clearly host factor and co-founding host responses will modulate disease susceptibility and natural *** is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling,progressive weakness,autonomic dysfunction,and *** injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy,whereas in acute motor axonal neuropathy membranes on the nerve axon(the axolemma)are the primary target for immune-related *** of GBS have been reported,most frequently related to Campylobacter jejuni infection,however,other agents such as Zika Virus have been strongly *** with GBS related to infections frequently produce antibodies against human peripheral nerve *** contrast,TM is an inflammatory disorder characterized by acute or subacute motor,sensory,and autonomic spinal cord *** is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to *** has been suggested to be triggered by infectious agents and molecular *** this review,we will focus on the putative role of infectious agents as triggering factors of GBS and TM.

关键词： bacterial infections disease outbreaks Guillain-Barrésyndrome transverse myelitis virus diseases Zika virus

Racial/ethnic disparities in hepatocellular carcinoma treatment and survival in California, 1988-2012

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World Journal of Gastroenterology 2016年第38期22卷 8584-8595页

作者： Susan L Stewart Sandy L Kwong Christopher L Bowlus Tung T Nguyen Annette E Maxwell Roshan Bastani eric W Chak Moon S Chen Jr Division of Biostatistics Department of Public Health SciencesUniversity of CaliforniaDavis School of Medicine Sacramenio CA 95817 United States California Department of Public Health Sacramenio CA 95817 United States Tung Division of Gastroenterology and Hepatology Department of Internal MedicineUniversity of CaliforniaDavis School of Medicine Sacramenio CA 95817 United States Division of General Internal Medicine University of California San Francisco CA 94101 United States UCLA Kaiser Permanente Center for Health Equity Fielding School of Public Health and Jonsson Comprehensive Cancer CenterUniversity of California Los Angeles CA 90095 United States Division of Hematology and Oncology Department of Internal MedicineUniversity of CaliforniaDavis School of MedicineSacramento CA 95817 United States Cancer Control/Cancer Health Disparities University of CaliforniaDavis Comprehensive Cancer CenterSacramento CA 95817 United States

AIM To describe racial/ethnic differences in treatment and survival among liver cancer patients in a populationbased cancer *** Invasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White(White, n = 12710), Hispanic(n = 8500), Chinese(n = 2723), non-Hispanic Black(Black, n = 2609), Vietnamese(n = 2063), Filipino(n = 1479), Korean(n = 1099), Japanese(n = 658), American Indian/Alaskan Native(AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian(n = 233), South Asian(n = 190), Hawai`ian/Pacific Islander(n = 172), Thai(n = 95), and Other Asian(n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause *** After adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio(OR) = 0.30, 95%CI: 0.17-0.53], Cambodian(OR = 0.65, 95%CI: 0.45-0.96), AIAN(OR = 0.66, 95%CI: 0.46-0.93), Black(OR = 0.76, 95%CI: 0.67-0.86), and Hispanic(OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese(OR = 1.58, 95%CI: 1.42-1.77), Koreans(OR = 1.45, 95%CI: 1.24-1.70), Japanese(OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese(OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio(HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians(HR = 1.35, 95%CI: 1.16-1.58), and Blacks(HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese(HR = 0.82, 95%CI: 0.77-0.86), Filipinos(HR = 0.84, 95%CI: 0.78-0.90), Vietnamese(HR = 0.85, 95%CI: 0.80-0.90), Koreans(HR = 0.90, 95%CI: 0.83-0.97), and Hispanics(H

关键词： Disparities Treatment Survival Liver cancer Hepatocellular carcinoma

Physiological and druggable skipping of immunoglobulin variable exons in plasma cells

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Cellular & Molecular Immunology 2019年第10期16卷 810-819页

作者： Mohamad Omar Ashi Nivine Srour Jean-Marie Lambert Anne Marchalot Ophelie Martin Sandrine Le Noir eric Pinaud Maria Victoria Ayala Christophe Sirac Jerome Sauliere Jerome Moreaux Michel Cogne Laurent Delpy Unite Mixte de Recherche Centre National de la Recherche Scientifique 7276 INSERM U1262-Controle de la Reponse Immune B et LymphoproliferationsUniversitede LimogesLimogesFrance Institute of Human Genetics CNRS-UM UMR9002Department of Biological HaematologyCHU MontpellierUniversity of MontpellierUFR MedecineMontpellierFrance Institut Universitaire de France Universitede LimogesLimogesFrance Present address:Lady davis Institute for Medical Research McGill University3755 Cote Ste-Catherine RoadMontrealQC H3T 1E2Canada

The error-prone V(D)J recombination process generates considerable amounts of nonproductive immunoglobulin(Ig)*** recently demonstrated that aberrant Ig chains lacking variable(V)domains can be produced after nonsense-associated altered splicing(NAS)***,the expression of these truncated Ig polypeptides heightens endoplasmic reticulum stress and shortens plasma cell(PC)*** questions remain regarding the molecular mechanisms underlying this new truncated Ig exclusion(TIE-)checkpoint and its restriction to the ultimate stage of B-cell *** address these issues,we evaluated the extent of NAS of Ig pre-mRNAs using an Ig heavy chain(IgH)knock-in model that allows for uncoupling of V exon skipping from TIE-induced *** found high levels of V exon skipping in PCs compared with B cells,and this skipping was correlated with a biallelic boost in IgH transcription during PC *** analysis further revealed that the skipped V exon turned into a ***,we showed that hypertranscription of Ig genes facilitated V exon skipping upon passive administration of splice-switching antisense oligonucleotides(ASOs).Thus,V exon skipping is coupled to transcription and increases as PC differentiation proceeds,likely explaining the late occurrence of the TIE-checkpoint and opening new avenues for ASO-mediated strategies in PC disorders.

关键词： Immunoglobulin Exon skipping Plasma cells Antisense Oligonucleotides Nonsense-associated altered splicing

Comprehensive review of autoantibodies in patients with hyper-IgM syndrome

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Cellular & Molecular Immunology 2018年第6期15卷 610-617页

作者： Mohamed-Ridha Barbouche Qubo Chen Marco Carbone Imen Ben-Mustapha Zakera Shums Mehdi Trifa Federica Malinverno Francesca Bernuzzi Haiyan Zhang Nourhen Agrebi Gary L Norman Christopher Chang M eric Gershwin Pietro Invernizzi Laboratory of Immunology Institute Pasteur de Tunis and Faculty of MedicineUniversity Tunis El Manar1002 TunisTunisia Humanitas Clinical and Research Center 20089 RozzanoItaly Clinical Laboratory Guangdong Provincial Hospital of Chinese medicine510000 GuangzhouChina Division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryUniversity of Milan-Bicocca20900 Monza(MB)Italy Department of Research and Development Inova Diagnostics92131 San DiegoCAUSA Department of Anesthesia and Intensive Care Children Hospital Bechir HamzaTunis and Faculty of MedicineUniversity Tunis El Manar1007 TunisTunisia Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthStateKey Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease200001 ShanghaiChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of California at Davis95616 DavisCAUSA

Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand *** CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary *** the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M ***,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood *** level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of *** immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the *** conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M *** presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.

关键词： immunoglobulin M autoantibodies immunodeficiency hyper-immunoglobulin M syndrome primary biliary cholangitis

The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis

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Cellular & Molecular Immunology 2017年第3期14卷 276-284页

作者： Takashi Tomiyama Guo-Xiang Yang Ming Zhao Weici Zhang Hajime Tanaka Jing Wang Patrick SC Leung Kazuiclli Okazaki Xiao-Song He Qianjin Lu Ross L Coppel Christopher L Bowlus M eric Gershwin Division of Rheumatology Allergy and Clinical Immunology University of California at Davis Davis CA 95616 USA Third Department of Internal Medicine Division of Gastroenterology and Hepatology Kansai Medical University Osaka 573-1191 Japan Hunan Key Laboratory of Medical Epigenomics Department of Dermatology The Second Xiangya Hospital Central South University Changsha Hunan 410011 People's Republic of China Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya 467-8601 Japan Department of Microbiology Monash University Melbourne Australia Division of Gastroenterology and Hepatology University of California at Davis School of Medicine. Sacramento. CA 95817. USA

Exosomes are nanoparticles of endocytic origin, secreted by a myriad of cell populations that are attracting increased attention by virtue of their ability to modulate cell-to-cell communications. They are also attracting attention in a variety of immunological issues, including autoimmunity and, in particular, their ability to regulate cytokine and chemokine activation. Primary biliary cirrhosis （PBC） is considered a model autoimmune disease, which has a highly focused cytotoxic response against biliary epithelial cells. We have isolated exosomes from plasma from 29 patients with PBC and 30 healthy controls （HCs）, and studied the effect of these exosomes on co-stimulatory molecule expression and cytokine production in mononuclear cell populations using an ex vivo system. We also identified the microRNA （miRNA） populations in PBC compared to HC exosomes. We report herein that although exosomes do not change cytokine production, they do significantly alter co-stimulatory molecule expression on antigen-presenting populations. Further, we demonstrated that CD86 up-regulated expression on CD14＋ monocytes, whereas CD40 up-regulated on CD11c＋ dendritic cells by exosomes from patients with PBC. In addition, there were differences of miRNA expression of circulating exosomes in patients with PBC. These data have significant importance based on observations that co-stimulatory molecules play a differential role in the regulation of T-cell activation. Our observation indicated that aberrant exosomes from PBC selectively induce expression of co-stimulatory molecules in different subset of antigen-presenting cells. These alterations may involve in pathogenesis of autoimmune liver disease.

关键词： autoimmunity exosome microRNA primary biliary cirrhosis

Identification and Antimicrobial Susceptibility of <i>Yersinia enterocolitica</i>Found in Chitterlings, Raw Milk and Swine Fecal Samples

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Advances in Microbiology 2018年第10期8卷 804-820页

作者： F. N. Drake S. davis J. Khatiwada L. Williams North Carolina A & T State University North Carolina Research Campus Kannapolis NC USA

Foodborne illness is an escalating concern upon public health. The prevalence of Yersinia enterocolitica was assessed in chitterlings, raw milk and swine fecal from North Carolina. Uncleaned thirty chitterling samples procured from a local grocery store, forty-five swine fecal samples, and forty unpasteurized cow milk samples supplied by the University farm were evaluated for the presence of Y. enterocolitica. Isolates identified as presumptive positive were characterized as colonies with a pink or deep-red center on MacConkey and CIN agar, and verified further through polymerase chain reaction (PCR) for the presence of 16S rRNA gene for the Yersinia genera. Results showed that 4.4% swine fecal samples, 7.5% milk samples and 11.3% chitterling samples were presumptive positive for Y. enterocolitica by the direct plating method on selective agars. Of the thirty-chitterling samples examined by PCR for the 16S rRNA gene, 26% samples contained the identification gene for the bacteria of interest. After conducting virulence tests, the fecal samples were revealed as non-pathogenic. Only one of the milk samples were considered pathogenic and consisted of the following virulent genes: Yersinia heat-stable toxin (yst), invasion (inv), attachment invasion locus (ail), virulence regulon transcriptional activator (virF), Yersinia adehesin A (yadA), and the O:3 antigen gene (rfbC). Seven out of the eight (87.5%) chitterling samples were shown to be pathogenic. Disc diffusion was conducted to determine the antimicrobial susceptibility of the isolates. Over half (55.5%) of the antimicrobial agents were found effective, with isolates being completely susceptible to ciprofloxacin, kanamycin, trimethoprim, cefotaxime, and gentamycin. Ampicillin was determined to be least effective, where 84.6% of the samples presented resistance to the drug. Random amplified polymorphic DNA (RAPD) analysis and eric-PCR techniques were used to evaluate genetic similarity among the Yersinia isolates. Th

关键词： Yersinia enterocolitica Polymerase Chain Reaction Antimicrobial

Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4^(+) T cells

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Cellular & Molecular Immunology 2020年第2期17卷 178-189页

作者： Zhi-Bin Zhao Fang-Ting Lu Hong-Di Ma Yin-Hu Wang Wei Yang Jie Long Qi Miao Weici Zhang Zhigang Tian William M.Ridgway Jie Cao M.eric Gershwin Zhe-Xiong Lian Department of General Surgery Guangzhou Digestive Disease CenterGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China Chronic Disease Laboratory Institutes for Life Sciences and School of MedicineSouth China University of TechnologyGuangzhou 510006China Institute of Immunology and School of Life Sciences University of Science and Technology of ChinaHefeiAnhui 230027China Center for Reproductive Medicine Anhui Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhuiChina Department of Gastroenterology and Hepatology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisCAUSA Division of Immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267USA

Liver-resident NK cells are distinct from conventional NK cells and play an important role in the maintenance of liver *** liver-resident NK cells participate in autoimmune cholangitis remains ***,we extensively investigated the impact of NK cells in the pathogenesis of autoimmune cholangitis utilizing the well-established dnTGFβRII cholangitis model,NK cell-deficient(Nfil3−/−)mice,adoptive transfer and in vivo antibody-mediated NK cell *** data demonstrated that disease progression was associated with a significantly reduced frequency of hepatic NK *** of NK cells resulted in exacerbated autoimmune cholangitis in dnTGFβRII *** further confirmed that the DX5−CD11c^(hi) liver-resident NK cell subset colocalized with CD4^(+) T cells and inhibited CD4^(+) T cell *** expression microarray analysis demonstrated that liver-resident NK cells had a distinct gene expression pattern consisting of the increased expression of genes involved in negative regulatory functions in the context of the inflammatory microenvironment.

关键词： Liver-resident NK Cholangitis CD4^(+)T cell Suppression

A roadmap for breeding orphan leafy vegetable species: a case study of Gynandropsis gynandra (Cleomaceae)

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Horticulture Research 2018年第1期5卷 903-917页

作者： E.O.Deedi Sogbohossou Enoch G.Achigan-Dako Patrick Maundu Svein Solberg Edgar M.S.Deguenon Rita H.Mumm Iago Hale Allen Van Deynze M.eric Schranz Biosystematics Group Wageningen UniversityPostbus 6476700APWageningenThe Netherlands Laboratory of Genetics Horticulture and Seed SciencesFaculty of Agronomic SciencesUniversity of Abomey-CalaviBP 2549Abomey-CalaviBenin Kenya Resource Center for Indigenous Knowledge(KENRIK) Centre for BiodiversityNational Museums of KenyaMuseum HillP.O.Box 40658Nairobi00100Kenya World Vegetable Center(AVRDC) P.O.Box 42ShanhuaTainan74199Taiwan NGO Hortitechs Developpement 02 BP 1111CotonouBenin Department of Crop Sciences University of IllinoisUrbana-ChampaignIL61801USA Department of Agriculture Nutritionand Food SystemsUniversity of New HampshireDurhamNH03824USA Department of Plant Sciences University of CaliforniaDavisCA95616USA

Despite an increasing awareness of the potential of“orphan”or unimproved crops to contribute to food security and enhanced livelihoods for farmers,coordinated research agendas to facilitate production and use of orphan crops by local communities are generally *** provide an overview of the current knowledge on leafy vegetables with a focus on Gynandropsis gynandra,a highly nutritious species used in Africa and Asia,and highlight general and species-specific guidelines for participatory,genomics-assisted breeding of orphan *** steps in genome-enabled orphan leafy vegetables improvement are identified and discussed in the context of Gynandropsis gynandra breeding,including:(1)germplasm collection and management;(2)product target definition and refinement;(3)characterization of the genetic control of key traits;(4)design of the‘process’for cultivar development;(5)integration of genomic data to optimize that‘process’;(6)multi-environmental participatory testing and end-user evaluation;and(7)crop value chain *** review discusses each step in detail,with emphasis on improving leaf yield,phytonutrient content,organoleptic quality,resistance to biotic and abiotic stresses and post-harvest management.

关键词： breeding crops cultivar