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IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome

Cellular & Molecular Immunology 2019年第12期16卷 921-931页

作者： Xiang Lin Xiaohui Wang Fan Xiao Kongyang Ma Lixiong Liu Xiaoqi Wang Dong Xu Fei Wang Xiaofei Shi Dongzhou Liu Yan Zhao Liwei Lu Department of Pathology and Shenzhen institute of Research and Innovation The University of Hong KongHong KongChina Department of rheumatology and Immunology Second Clinical Medical College of Jinan UniversityShenzhen People’s HospitalShenzhenChina Department of rheumatology Peking Union Medical College HospitalBeijingChina Department of rheumatology The First Affiliated Hospital and College of Clinical MedicineHenan University of Science and TechnologyLuoyangChina

Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.

关键词： Primary Sjögren’s syndrome T follicular helper cells Breg cells

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Supplying the trip to antibody production-nutrients,signaling,and the programming of cellular metabolism in the mature B lineage

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Cellular & Molecular Immunology 2022年第3期19卷 352-369页

作者： Mark R.Boothby Shawna K.Brookens Ariel L.Raybuck Sung Hoon Cho Department of Pathology Microbiology&ImmunologyMolecular Pathogenesis DivisionVanderbilt University Medical CenterNashvilleTN37232USA Department of Medicine Rheumatology&Immunology DivisionVanderbilt University Medical CenterNashvilleTN37232USA Cancer Biology Program Vanderbilt UniversityNashvilleTN37232USA Vanderbilt institute of Infection Inflammationand ImmunologyNashvilleTN37232USA

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody(Ab)secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection.With this backdrop,it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise,persist,and meet the challenge of secreting vast amounts of these glycoproteins.Whereas plasmablasts and plasma cells(PCs)are the primary sources of secreted Abs,the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates.At each step,cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients.Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription,translation,and metabolism.This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion.Salient findings of this group and others,sometimes exhibiting differences,will be summarized with regard to the journey to a distinctive metabolic program in PCs.

关键词： B lymphocyte Plasma cell Intermediary metabolism Glucose Glutamine Fatty acid Signal transduction

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Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population

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Chinese Medical Journal 2011年第18期124卷 2863-2867页

作者： LU Xiao-lan ZHOU Xu-jie GUO Jian-ping JIA Ru-lin ZHAO Yi JIANG Quan LIU Xiang-yuan LIU Yi SUN Ling-yun ZHANG Hong LI Zhan-guo Department of rheumatology and Immunology Peking University People's Hospital Beijing 100044 China Renal Division Peking University First Hospital Peking University Institute of Nephrology Key Laboratory of Renal Disease Ministry of Health of China Beijing 100034 China Department of rheumatology Xuanwu Hospital Capital Medical University Beijing 100053 China Department of rheumatology Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China Department of rheumatology and Immunology Peking University Third Hospital Beijing 100191 China Department of rheumatology West China Hospital Sichuan University Chengdu Sichuan 610041 China Department of rheumatology Drum Tower Hospital Nanjing University Medical School Nanjing Jiangsu 210008 China

Background A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis （RA） in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population. Methods We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism （SNP） with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors （RF） and anti-cyclic citrullinated peptides （anti-CCP） antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data. Results No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 （C/T） polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population. Conclusions Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.

关键词： rheumatoid arthritis PRDM1/ATG5 genetic association Chinese Han population

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Human leukocyte antigen B polymorphism and association between HLA-B27 and endoplasmic reticulum aminopeptidase 1 rs30187 SNP in patients with ankylosing spondylitis in Bangladesh

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rheumatology & Autoimmunity 2022年第1期2卷 15-21页

作者： Md Kamrul H.Sajib Shamim Ahmed Syed A.Haq Minhaj R.Choudhury Mohammed Uddin Furkan Uddin Muhammad S.A.Khan Mohammad M.Zaman Department of rheumatology Dhaka Medical College HospitalDhakaBangladesh Department of rheumatology Bangabandhu Sheikh Mujib Medical UnivesityDhakaBangladesh Department of Human Genetics Mohammed Bin Rashid University of Medicine and Health SciencesCollege of MedicineDubaiUAE Genetics and Genomic Department NeuroGen HealthcareDhakaBangladesh Department of Medicine Sheikh Hasina Institute of Burn and Plastic SurgeryDhakaBangladesh Advisor(Research and Publication) World Health OrganizationDhakaBangladesh

Objectives:To determine the association of Human leukocyte antigen B(HLA‑B)alleles with ankylosing spondylitis and the allelic association of HLAB27 with endoplasmic reticulum aminopeptidase 1(ERAP1)single-nucleotide polymorphism(SNP)rs30187 in patients with ankylosing spondylitis(AS).Methods:We studied 48 consecutively enrolled well-defined AS patients and 48 healthy controls recruited from the outpatient clinic of the rheumatology department of Bangabandhu Sheikh Mujib Medical University(BSMMU),Dhaka,Bangladesh.To genotype HLA-B alleles from peripheral blood DNA,we designed sequence-specific primers for polymerase chain reaction.Sanger's sequencing method was used to detect the ERAP1 rs30187 SNP.The HLA-B allele distributions were compared between cases and controls.To infer an allelic association between HLA-B27 and ERAP1,allele distributions from both loci were compared using cross-tabulations.Chi-squared test or Fisher's exact test was used to quantify the association,and their strength of association was tested by odds ratio(OR)with 95%confidence interval(CI).Results:The frequency of HLA-B27 was found to be higher in AS patients(60.4%)than in healthy controls(8.3%).HLA-B27 allele had an OR of 16.8(95%CI=5.2–54.4)for the development of AS.Overall,4%of AS patients had both HLA-B27 and HLA-B40.No significant association was found between ERAP1 rs30187 SNP and HLA-B27 in patients with AS(OR=1.7,95%CI=0.5–5.6).Conclusions:HLA-B27 was significantly associated with AS in patients in Bangladesh.However,no association between ERAP1 rs30187 SNP and HLA-B27 was observed.

关键词： AS Bangladesh ERAP1 rs30187 SNP HLA-B HLA-B27

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Developing hierarchical microneedles for biomedical applications

再生工程(英文)

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再生工程(英文) 2023年第3期4卷 316-327页

作者： Minhui Lu Xiaoxuan Zhang Zhiqiang Luo Yuanjin Zhao Department of rheumatology and Immunology Nanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325001China

As a new kind of microcarrier device,microneedles are featured by micrometer needle arrays with an overall size in the centimeter scale.Due to the needle shape and the micron size,microneedles can penetrate the skin without harming nerves and blood vessels,which causes many advantages such as minimally invasive,safe and convenient.The past few decades have witnessed a great leap in microneedles research.The main materials of microneedles have changed from metal and ceramic to polymers with more complex functions,and the optimiza-tion of materials and preparation strategies has led to a greater variety of microneedle styles.Among them,the construction or combination of smaller size structures or materials on microneedles to fabricate hierarchical mi-croneedles is a major research hotspot.Here,we present the recent research progress of hierarchical microneedles for biomedicine.We begin by discussing the fabrication strategies of hierarchical microneedles,including main-stream casting and coating methods based on microneedle molds and three dimensions(3D)printing methods.We then expand the discussion from the hierarchical microneedles with porous structure to those composited with nanomaterials.Eventually,we have a discussion about the research progress of hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery,as well as its future development direction.

关键词： Microneedle Porous structure Nanomaterials Drug delivery Detection

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Increased levels of lactate dehydrogenase and hypertension are associated with severe illness of COVID-19

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World Journal of Clinical Cases 2022年第1期10卷 128-135页

作者： Zhen-Mu Jin Ji-Chan Shi Mo Zheng Que-Lu Chen Yue-Ying Zhou Fang Cheng Jing Cai Xian-Gao Jiang Department of rheumatology Immunology and AllergyWenzhou Central HospitalThe Second Affiliated Hospital of Shanghai UniversityAffiliated Dingli Clinical Institute of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Infectious Diseases Wenzhou Central HospitalThe Second Affiliated Hospital of Shanghai UniversityAffiliated Dingli Clinical Institute of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Radiology Wenzhou Central HospitalThe Second Affiliated Hospital of Shanghai UniversityAffiliated Dingli Clinical Institute of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND Coronavirus disease 2019(COVID-19)is amid an ongoing pandemic.It has been shown that patients with cardiovascular comorbidities are at higher risk of severe illness of COVID-19.AIM To find out the relationship between cardiovascular comorbidities and severe illness of COVID-19.METHODS The clinical data of 140 COVID-19 patients treated from January 22,2020 to March 3,2020 at our hospital were retrospectively collected.The clinical characteristics were compared between patients with mild illness and those with severe illness.RESULTS There were 75 male patients and 65 female patients(53.6%vs 46.4%).The mean age was 45.4±14.6 years(range,2-85 years).Most of the patients had mild illness(n=114,81.4%)and 26 patients had severe illness(18.6%).The most common symptom was fever(n=110,78.6%),followed by cough(n=82,58.6%)and expectoration(n=51,36.4%).Eight patients were asymptomatic but were positive for severe acute respiratory syndrome coronavirus 2 RNA.Patients with severe illness were significantly more likely to be hypertensive than those with mild illness[(10/26,38.4%)vs(22/114,19.3%),P=0.036].The levels of lactate dehydrogenase were significantly higher in the severe illness group than in the mild illness group(299.35±68.82 vs 202.94±63.87,P<0.001).No patient died in either the severe illness or the mild illness group.CONCLUSION Hypertension and elevated levels of lactate dehydrogenase may be associated with severe illness of COVID-19.

关键词： Pneumonia Virus COVID-19 Hypertension Lactate dehydrogenase Radiology

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Aquaculture derived hybrid skin patches for wound healing

再生工程(英文)

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再生工程(英文) 2023年第1期4卷 28-35页

作者： Xinyue Cao Lingyu Sun Zhiqiang Luo Xiang Lin Yuanjin Zhao Department of rheumatology and Immunology School of Biological Science and Medical EngineeringNanjing Drum Tower HospitalSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325001China

Natural biomaterials have been widely applied in wound treatment.Hotspots in this area are focused on reducing their immunogenicity and improving their therapeutic effect.In this work,we present a novel aquaculture de-rived hybrid skin patch based on acellular fish skin(AFS)and chitosan(CS)for wound healing.Such functional patch was simply constructed by infiltrating the vascular endothelial growth factor(VEGF)-loaded CS pregel into the porous scaffold of the AFS.As the natural molecules and structure of fish skin are well-retained dur-ing the synthesis processes,the final patch presented brilliant tensile property,water-absorption property,good biocompatibility and low immunogenicity.In addition,the integrated CS and VEGF endow the patch with an-tibacterial and angiogenesis capability respectively for promoting tissue growth and wound healing.Thus,in a full-thickness wound rat model,the hybrid patch has been demonstrated with dramatic therapeutic efficacy in inhibiting inflammatory,accelerating angiogenesis,collagen deposition,and tissue generation during the wound repair procedure.These features imply the practical value of this multifunctional aquaculture derived hybrid skin patch in clinical wound management.

关键词： Wound healing Patch Fish skin Bioactive Biomaterial

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Targeted treatment strategy for patients with severe pulmonary hypertension secondary to connective tissue diseases

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rheumatology & Autoimmunity 2023年第3期3卷 157-165页

作者： Bo Jiang Chun Wang Yansheng Jin Guanjun Guo Kangxing Zhou Xuebing Feng Genhong Yao Department of rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsuChina Department of rheumatology and Immunology Wuzhong People's HospitalSuzhouJiangsuChina Department of Cardiac Ultrasound The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsuChina

Background:Pulmonary arterial hypertension(PAH)associated with connective tissue diseases(CTD)(CTD-PAH)remains a difficult challenge in clinical practice.We aimed to evaluate the effects of targeted vasodilators in patients with severe CTD-PAH.Methods:The data of 53 patients with severe CTD-PAH hospitalized at the Department of rheumatology and Immunology,The Affiliated Drum Tower Hospital of Nanjing University Medical School,were retrospectively reviewed.Patients were followed up for an average of 2 years to track their outcomes.The efficacy of treatment and the survival rate of patients with severe CTD-PAH were determined.Results:Among the causes of severe CTD-PAH,systemic lupus erythematosus(SLE)was the most common(39.6%),and the age at onset in patients with SLE-PAH was younger than that of patients with other CTD.Bosentan was more effective than sildenafil in reducing pulmonary artery pressure,improving cardiac function,and increasing survival time.Combination therapy with targeted vasodilators significantly improved the prognosis of patients with severe CTD-PAH compared with monotherapy.Conclusions:Patients with severe CTD-PAH should be treated early with targeted vasodilators.In this study,bosentan was superior to sildenafil.Combined treatment might be an option for severe CTD-PAH.

关键词： connective tissue disease pulmonary arterial hypertension systemic lupus erythematosus targeted vasodilator

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Significance of dormant forms of Helicobacter pylori in ulcerogenesis

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World Journal of Gastroenterology 2017年第27期23卷 4867-4878页

作者： Vasiliy Ivanovich Reshetnyak Tatiana Magomedalievna Reshetnyak VA Negovsky Research institute of General Reanimatology of Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology Department of Systemic Connective Tissue Diseases VA Nasonova Research Institute of Rheumatology

Nearly half of the global population are carriers of Helicobacter pylori(H. pylori),a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease(PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However,the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms,but also contribute to the conversion of H. pylori into the resting(dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms,such as S-shaped,C-shaped,U-shaped,and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.

关键词： Helicobacter pylori H 的形式。pylori H 的休眠形式。pylori H 的可行形式。pylori H 的不能生存的形式。pylori H 的生理的状态。pylori H 的 Culturable 形式。pylori H 的 Unculturable 形式。pylor 休眠 H 的复活。pylori Ulcerogenesis

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Associations of autoantibodies and clinical profile of the patients with systemic sclerosis

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rheumatology & Autoimmunity 2022年第3期2卷 141-149页

作者： Shahin Mahmud Minhaj R.Choudhury Iftekhar H.Bandhan Md.Sahidul Islam MdAbu Shahin Syed A.Haq Mohammad M.Zaman Department of Clinical Neurology National Institute of Neurosciences and HospitalAgargaonDhakaBangladesh Department of rheumatology Bangabandhu Sheikh Mujib Medical UniversityDhakaBangladesh Data Management World Health OrganizationDhakaBangladesh Research and Publication World Health OrganizationDhakaBangladesh

Background:Systemic sclerosis is characterized by the involvement of organs and the presence of specific antibodies.The objectives of this study were to identify the autoantibodies and to determine their association with the selected clinical features of the disease among Bangladeshi systemic sclerosis patients.Methods:This cross-sectional study was performed at the rheumatology outpatient clinic of Bangabandhu Sheikh Mujib Medical University.Autoantibodies against nine systemic sclerosis-specific antigens were tested using an enzyme-linked immunoassay immunoblot kit.Several clinical features of patients with positive and negative autoantibody were examined by χ^(2) or Fisher's exact tests.Results:A total of 71 patients with systemic sclerosis(66;93.0%female)were included.Their mean age at disease onset was 33.2 years.Fifty-seven(80.3%)patients had diffuse cutaneous subtype.Out of nine autoantibodies,four were positive,anti-topoisomerase-I(57.7%),anti-U1 ribonucleic protein(21.1%),anti-RNA polymerase Ⅲ(18.3%),and anticentromere antibodies(4.2%).Eleven(15.5%)patients were negative for any antibodies and 11 patients were positive for at least two autoantibodies.Anti-U3-RNP,anti-PMScl,anti-Ku,and anti-Th/To auto antibodies were absent in all patients.Anti-RNA polymerase III was associated with raised pulmonary arterial systolic pressure(PASP)and anti-U1-RNP with decreased forced vital capacity(FVC).Conclusions:Anti-topoisomerase-I was the commonest autoantibody in patients with systemic sclerosis in Bangladesh.Anti-RNA polymerase III antibody had significant association with raised PASP and anti-U1-RNP with decreased FVC.

关键词： autoantibodies clinical profile systemic sclerosis

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