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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim Department of immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:immunology and Microbiology Graduate program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTEN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons Teresa Fuster Isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel Laura Valle Hereditary Cancer program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain Department of immunology and Oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid 28029Spain Catalan Institute of Oncology IDIBGiGirona 17007Spain Division of Clinical Cancer Genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an E3 ubiquitin ligase that antagonizes PTEN tumor suppressive function,have been proposed as an alternative mechanism of PTEN inactivation in PTEN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTEN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

Emerging microfluidics for the modeling and treatment of arthritis

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Engineered Regeneration 2024年第2期5卷 153-169页

作者： Nengjie Yang Chi Sun Chen Dong Yuting Huang Yujuan Zhu Zhifeng Gu Department of Rheumatology Research Center of ImmunologyAffiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China Department of Geriatrics Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China research Center of Clinical Medicine Research Center of ImmunologyAffiliated Hospital of Nantong UniversityNantong 226001China

Microfluidic is a technology that allows the precise control of fluid in a *** its advantages of high throughput and low cost,microfluidic technology has achieved good performance in various fields in recent *** is a general term for a variety of joint diseases,which can be clinically manifested as joint pain and swelling,seriously affecting people’s physical and mental *** present,the causes of arthritis disease are still unknown,and existing disease models and treatment methods are still limited,so more treatments need to be *** organ chip is a cutting-edge technology to build a bionic human organ model,which can reflect the structure and function characteristics of human organs by simulating the physiological environment of tissues and cells in *** paper reviews the application of microfluidic technology in the modeling and treatment of arthritis,hoping to open up a new vision for the study of arthritis.

关键词： Microfluidics Arthritis Organ on a chip Drug delivery system Drug screening

Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer immunology program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

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Cancer Biology & Medicine 2024年第6期21卷 513-540页

作者： Zhihong Luo Xiaohua Huang Xinyi Xu Kefeng Wei Yi Zheng Ke Gong Wenhua Li Hubei Key Laboratory of Cell Homeostasis College of Life SciencesWuhan UniversityWuhan 430072China Wuhan University Shenzhen research Institute Shenzhen 518057China Central Laboratory University of Chinese Academy of Sciences-Shenzhen HospitalShenzhen 518107China Hubei Province Key Laboratory of Allergy and immunology and Department of immunology School of Basic Medical SciencesWuhan UniversityWuhan 430071China

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains ***: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell ***: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some ***: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regula

关键词： Breast cancer lactate dehydrogenase B lactic acid NK cells tumor immunity

The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao Department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

Interleukins in Epilepsy:Friend or Foe

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Neuroscience Bulletin 2024年第5期40卷 635-657页

作者： Yuan Dong Xia Zhang Ying Wang Neuropsychiatry research Institute The Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao266000China program in Cellular and Molecular Medicine Boston Children’s HospitalBostonMA02115USA

Epilepsy is a chronic neurological disorder with recurrent unprovoked seizures,affecting~65 million *** in patients with epilepsy and animal models suggests a contribution of neuroinflammation to epileptogenesis and the development of ***(ILs),as one of the major contributors to neuroinflammation,are intensively studied for their association and modulatory effects on ictogenesis and *** are commonly divided into pro-and anti-inflammatory cytokines and therefore are expected to be pathogenic or neuroprotective in ***,both protective and destructive effects have been reported for many *** may be due to the complex nature of ILs,and also possibly due to the different disease courses that those ILs are involved *** this review,we summarize the contributions of different ILs in those processes and provide a current overview of recent research advances,as well as preclinical and clinical studies targeting ILs in the treatment of epilepsy.

关键词： Epilepsy Interleukins Neuroinflammation

Spatio-temporal coupled mode theory for nonlocal metasurfaces

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Light(Science & Applications) 2024年第2期13卷 267-282页

作者： Adam Overvig Sander A.Mann Andrea Alù Photonics Initiative Advanced Science Research CenterCity University of New YorkNew YorkNY10031USA Physics program Graduate Center of the City University of New YorkNew YorkNY10016USA

Diffractive nonlocal metasurfaces have recently opened a broad range of exciting developments in nanophotonics research and applications,leveraging spatially extended—yet locally patterned—resonant modes to control light with new degrees of *** conventional grating responses are elegantly captured by temporal coupled mode theory,current approaches are not well equipped to capture the arbitrary spatial response observed in the nascent field of nonlocal ***,we introduce spatio-temporal coupled mode theory(STCMT),capable of elegantly capturing the key features of the resonant response of wavefront-shaping nonlocal *** framework can quantitatively guide nonlocal metasurface design while maintaining compatibility with local metasurface frameworks,making it a powerful tool to rationally design and optimize a broad class of ultrathin optical *** validate this STCMT framework against full-wave simulations of various nonlocal metasurfaces,demonstrating that this tool offers a powerful semi-analytical framework to understand and model the physics and functionality of these devices,without the need for computationally intense full-wave *** also discuss how this model may shed physical insights into nonlocal phenomena in photonics and the functionality of the resulting *** a relevant example,we showcase STCMT’s flexibility by applying it to study and rapidly prototype nonlocal metasurfaces that spatially shape thermal emission.

关键词： theory resonant spatially

Accuracy and precision of dried urine spot method for the detection of Schistosoma mansoni circulating cathodic antigens in resource-limited settings

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Infectious Diseases of Poverty 2024年第1期13卷 103-104页

作者： Abdallah Zacharia Clemence Kinabo Twilumba Makene Huda Omary George Ogweno Faraja Lyamuya Billy Ngasala Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania National Institute for Medical research Mwanza Tanzania Neglected Tropical Diseases Control program Ministry of Health Dodoma Tanzania

Background The World Health Organization recommends the use of Schisto point-of-care circulating cathodic anti-gens(Schisto POC-CCA)for screening of Schistosoma mansoni as it offers better sensitivity than ***,there are limitation facing the use of this method including timely availability of the test *** aim of this study was to determine the reliability of dried urine spot(DUS)method for collection of urine and detection of *** using Schisto POC-CCA cassettes in a resource-limited *** A cross-sectional study was conducted between October and November 2022 among 250 primary school children in Sengerema District,northwestern *** CCA was detected in filter paper-based DUSs,liquid urine using DUS Schisto POC-CCA(index),and direct urine Schisto POC-CCA(comparator)methods *** eggs in stool were detected using duplicate Kato-Katz(KK)*** measures of accuracy were com-puted and compared between the index and comparator *** strength of agreement between inter-raters precisions was tested using Cohen's kappa(k).Results This study revealed *** prevalence rates of 28.8%,54.0%and 50.8%by duplicate KK,direct urine Schisto POC-CCA and DUS Schisto POC-CCA methods *** mean intensity of infection among infected participants Was 86.3 eggs per gram of stool(EPG)ranging from 12.0 EPG to 824.0 *** sensitivity of DUS Schisto POC-CCA and direct urine Schisto POC-CCA Was 94.44%(95%CI:89.15-99.74%)and 97.22%(95%CI:93.43-100.00%)*** DUS Schisto POC-CCA method had slightly higher specificity(66.85%)than direct urine Schisto POC-CCA method(63.48%).The accuracy of the DUS Schisto POC-CCA Was found to be slightly high(74.80%,95%CI:68.94-79.06%)compared to that of direct urine Schisto POC-CCA(73.20%,95%CI:67.25-78.59%).There was good agreement between two laboratory technologists who performed the DUS Schisto POC-CCA method on similar samples(k=0.80,95%CI:0.59-0.95).Con

关键词： Accuracy Point-of-care circulating cathodic antigen Dried urine spot Schistosoma mansoni Sensiti Specificity