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Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells

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Cellular & Molecular Immunology 2020年第8期17卷 843-855页

作者： Joanne Boldison Larissa Camargo Da Rosa Joanne Davies Li Wen F.Susan Wong division of infection and immunity Cardiff University School of MedicineCardiffCF144XNUK Section of Endocrinology School of MedicineYale UniversityYaleCT06520USA

Regulatory B cells(Bregs)suppress and reduce autoimmune ***,given the variety of Breg subsets,the role of Bregs in the pathogenesis of type 1 diabetes is still ***,we dissect this fundamental *** show that natural protection from type 1 diabetes in nonobese diabetic(NOD)mice is associated with increased numbers of IL-10-producing B cells,while development of type 1 diabetes in NOD mice occurs in animals with compromised IL-10 production by B ***,B cells from diabetic mice regain IL-10 function if activated by the innate immune receptor TLR4 and can suppress insulin-specific CD8 T cells in a dendritic cell(DC)-dependent,IL-10-mediated *** of CD8 T cells is reliant on B-cell contact with *** cell contact results in deactivation of DCs,inducing a tolerogenic state,which in turn can regulate pathogenic CD8 T *** findings emphasize the importance of DC–Breg interactions during the development of type 1 diabetes.

关键词： Regulatory B cells type 1 diabetes IL-10 Dendritic cells

From Entry to Evasion:A Comprehensive Analysis of Host-Virus Interactions for Monkeypox

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Infectious Microbes & Diseases 2024年第2期6卷 56-64页

作者： Vahideh Hamidi Sofiani Mohammad Rezaei Zadeh Rukerd Javad Charostad Mohammad Pardeshenas Reza Ghazi Nasir Arefinia Sara Shafieipour Faranak Salajegheh Mohsen Nakhaie Department of Microbiology Golestan University of Medical SciencesGorganIran Gastroenterology and Hepatology research Center Institute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran Universal Scientific Education and research Network(USERN) TehranIran Department of Microbiology Faculty of MedicineShahid Sadoughi University of Medical SciencesYazdIran Department of Microbiology School of MedicineKerman University of Medical SciencesKermanIran Department of Biotechnology Golestan University of Medical SciencesGorganIran Student research Committee Jiroft University of Medical SciencesJiroftIran Physiology research Center Institute of NeuropharmacologyKerman University of Medical SciencesKermanIran Clinical research Development Unit School of MedicineAfzalipour HospitalKerman University of Medical SciencesKermanIran

Monkeypox(Mpox)has posed a novel challenge and emerged as a threat to global public health since the onset of its outbreak in *** is spreading throughout the world in both endemic and non-endemic countries,indicating that its behavior is *** prevalence of Mpox and the risk of a global pandemic necessitate a better understanding of Mpox virus replications and interactions with the ***,we attempted to provide a detailed comprehensive review of Mpox virus behavior at the molecular level from the entry level to the establishment of a successful infection,including attachment and entry,DNA replication,protein expression and viron assembly and *** review also describes its strategies to evade host immune responses and inhibit apoptosis,and uncovers underlying molecular mechanisms such as subverted signaling pathways and cellular factors behind host-viral interactions.

关键词： monkeypox immunity apoptosis virus-host interaction

Langerin (CD207) represents a novel interferon-stimulated gene in Langerhans cells

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Cellular & Molecular Immunology 2020年第5期17卷 547-549页

作者： Ghizlane Maarifi Magdalena A.Czubala Justine Lagisquet Matthew O.Ivory Kyra Fuchs Laure Papin James C.Birchall Sébastien Nisole Vincent Piguet Fabien P.Blanchet Institut de Recherche en Infectiologie de Montpellier(IRIM) Universitéde MontpellierCNRSMontpellierFrance systems immunity university research institute and division of infection and immunity Cardiff University School of MedicineHeath ParkCardiffUK School of Pharmacy and Pharmaceutical Sciences Cardiff UniversityCardiffUK division of Dermatology Women’s College HospitalTorontoCanada division of Dermatology Department of MedicineUniversity of TorontoTorontoCanada

Interferons(IFNs)are“warning signal”cytokines released upon pathogen *** control the expression of interferonstimulated genes(ISGs),which are often crucial to restrict viral infections and establish a cellular antiviral state.1,2 Langerin(CD207),a well-known surface receptor on Langerhans cells(LC),belongs to the C-type lectin receptor(CLR)family and constitutes a major pathogen binding receptor able to regulate both innate and adaptive immune responses.3,4 Importantly,this CLR was reported as an antiviral receptor.

关键词： Langerhans interferon belongs

Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim Jennifer E.Kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent J.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietje Justin Teeguarden Kristin E.Burnum-Johnson Biological Sciences division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism immunity

The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 701-710页

作者： Minjie Wu Heng Dong Chao Xu Mengqing Sun Haojin Gao Fangtian Bu Jianxiang Chen College of Pharmacy and Department of Hepatology Institute of Hepatology and Metabolic DiseasesThe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer CentreSingapore 169610Singapore Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin ***,increasing evidences indicate that BCL9 also plays multiple Wnt-independent ***,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological ***,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

关键词： BCL9 Development immunity Multifaceted functions Therapeutic target Tumorigenesis

Anti-TOSO antibody treatment promotes T cell activation-induced cell death(AICD) in vitro and in vivo

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Chinese Science Bulletin 2014年第13期59卷 1374-1385页

作者： Yi Tan Xue Han Xiaoran Wu Qiao Xing Lieping Chen Shengdian Wang Key Laboratory of infection and immunity Institute of Biophysics Chinese Academy of Sciences university of Chinese Academy of Sciences Department of Immunobiology Yale University School of Medicine

T cell activation-induced cell death(AICD),that involves the induction of Fas-mediated apoptosis,is very important for the maintenance of immune *** was firstly described as an inhibitor of Fasmediated apoptosis and overexpressed in chronic lymphocytic ***,TOSO was identified as IgM *** this study,we produced anti-TOSO monoclonal antibody(mAb)that could block the binding of IgM to TOSO and found that T cell apoptosis is negatively correlated with TOSO expression during T cell *** of activated T cells with anti-TOSO blocking mAb promoted T cell AICD in in vitro AICD model,and treatment of xenogeneic-GVHD mice with the antibody also increased the sensitivity of activated T cells to Fasinduced apoptosis,which was accompanied by reduction of c-FLIPL expression and up-regulation of AP-1 *** summary,our data indicate the anti-apoptotic effect of TOSO in T cell AICD and open up new therapeutic prospects for the treatment of hematologic malignancies and immune disorders.

关键词： T细胞活化单克隆抗体细胞死亡治疗诱导体外 Fas介导淋巴细胞白血病

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina university of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

Using intersectional gender analysis to identify challenges in tuberculosis care at four health care facilities in Uganda

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Infectious Diseases of Poverty 2024年第1期13卷 91-91页

作者： Winters Muttamba Samson Omongot Irene Najingo Roseline Nuwarinda Esther Buregyeya Mariam Otmani del Barrio Rosemary Morgan Bruce Kirenga Sarah Ssali Makerere university Lung institute Makerere University Kampala Uganda division of infection and Global Health School of Medicine University of St Andrews St. Andrews UK Infectious Disease institute Makerere University Kampala Uganda School of Public Health Makerere University Kampala Uganda UNICEF UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) World Health Organization Geneva Switzerland Johns Hopkins Bloomberg School of Public Health Baltimore MD USA School of Women and Gender Studies Makerere University Kampala Uganda

Background Tuberculosis(TB)care could be considered as a continuum from symptom recognition,decision to seek care,diagnosis,treatment initiation and treatment completion,with care along the continuum influenced by several *** dimensions could influence TB care,and indeed,more men than women are diagnosed with TB each *** study was done to identify social stratifiers that intersect with gender to influence TB *** A cross-sectional qualitative study was done at four health facilities in 3 districts in central Uganda between October 2020 and December *** was collected from patients seeking a diagnosis or on TB treat-ment through focus group discussions and key informant *** themes around gender guided by a gender and intersectionality lens were developed and thereafter thematic content analysis was *** Women have increased vulnerability to TB due to bio mass exposure through roles like *** have increased access to health care services as they interface with the health care system frequently given their role as child bearers and child care *** have a duty to provide for their families and this most often is prioritised over healthcare seeking,and together with belief that they are powerful beings leads to poor healthcare seeking hab-its and delays in healthcare *** on when and where to seek care were not straightforward for women,who most often rely on their husbands/partners to make *** Men and women experience challenges to TB care,and that these challenges are deeply rooted in roles assigned to them and further compounded by *** challenges need to be addressed through intersec-tional gender responsive interventions if TB control is to be improved.

关键词： Tuberculosis Gender Intersectionality Masculinity

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed

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Infectious Diseases of Poverty 2024年第1期13卷 85-89页

作者： Robert Colebunders Joseph Nelson Siewe Fodjo Olivia Kamoen Luis-Jorge Amaral Amber Hadermann Chiara Trevisan Mark J.Taylor Julia Gauglitz Achim Hoerauf Yasuaki Sato Katja Polman Maria-Gloria Basanez Dan Bhwana Thomson Lakwo Gasim Abd-Elfarag Sebastien D.Pion Global Health institute University of AntwerpAntwerpBelgium Department of Neurology Heilig Hart ZiekenhuisLierBelgium Department of Public Health Institute of Tropical MedicineAntwerpBelgium Liverpool School of Tropical Medicine LiverpoolUK Department of Computer Science University of AntwerpAntwerpBelgium institute of Medical Microbiology Immunology and ParasitologyUniversity Hospital BonnBonnGermany German Center for infection research(DZIF) Partner Site Bonn-CologneBonnGermany School of Global Humanities and Social Sciences Nagasaki UniversityNagasakiJapan MRC Centre for Global Infectious Disease Analysis and London Centre for Neglected TropicalDisease research Department of Infectious Disease EpidemiologySchool of Public HealthImperial College LondonLondonUK National institute for Medical research TangaTanzania Vector Control division Ministry of HealthKampalaUganda School of Public Health University of JubaJubaSouth Sudan Access for Humanity JubaSouth Sudan French National research institute for Sustainable Development MontpellierFrance

Background There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health *** text During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with *** To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

关键词： Onchocerciasis Morbidity Burden of disease Prevention Ivermectin Epilepsy Nodding syndrome Treatment Children Policy