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Cellular & molecular immunology 2024年第4期21卷 409-411页

作者： Dieter Kabelitz institute of immunology University of KielKielGermany

Members of the butyrophilin(BTN)family of transmembrane molecules play an important role in the activation of humanγδT cells.In recent years,it has been discovered that BTN3A1 and BTN2A1 are indispensable in this process,but other members like BTN3A2 and BTN3A3 are also required.So far,very little is known about the transcriptional and post-translational regulation of BTN expression.

关键词： expression. insight critical

Transcriptomic and pathological profiling of a new congenic mouse model with Lepr mutation:Evaluating susceptibility to the development of obesity and NAFLD

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Genes & Diseases 2024年第3期11卷 34-38页

作者： MJ Mahesh Kumar Shailendra Arindkar Masum Saini Perumal Nagarajan National institute of immunology New Delhi 100067India Center for Cellular and molecular Biology Hyderabad 500007India Regional Center for Biotechnology Faridabad 121001India

Non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)are two disease conditions for which obesity is a risk factor.^(1)Due to the close relationship between the three pathologies,researchers frequently use the same mouse models to identify the underlying processes of obesity,NAFLD,and T2DM.For instance,leptin(Lep)-null(ob/ob)and leptin receptor(Lepr)-deficient(db/db)mice spontaneously develop NAFLD and show different phenotypes of extreme obesity and diabetes,respectively.

关键词： obesity NAFLD Lep

Emerging role of galectin 3 in neuroinflammation and neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 2004-2009页

作者： Brian M.Lozinski Khanh Ta Yifei Dong Department of clinical Neuroscience University of CalgaryCalgaryABCanada Deparment of Biochemistry Microbiology&ImmunologyUniversity of SaskatchewanSaskatoonSKCanada

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

关键词： Alzheimer’s disease Galectin 3 microglia multiple sclerosis neurodegeneration neuroinflammation Parkinson’s disease therapeutics

Cryo-EM structure of cannabinoid receptor CB1-β-arrestincomplex

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Protein & Cell 2024年第3期15卷 230-234页

作者： Yuxia Wang Lijie Wu Tian Wang Junlin Liu Fei Li Longquan Jiang Zhongbo Fan Yanan Yu Na Chen Qianqian Sun Qiwen Tan Tian Hua Zhi-Jie Liu iHuman institute ShanghaiTech UniversityShanghai 201210China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China institute of molecular and clinical Medicine Kunming Medical UniversityKunming 650500China

Dear Editor,G protein-coupled receptors(GPCRs)play a vital role in regulating almost every aspect of human physiology,making up more than one-third of marketed drug targets(Santos et al.,2017).GPCRs orchestrate their signalling through interactions with three distinct downstream protein families:G proteins,G protein-coupled receptor kinases(GRKs),and arrestins(Santos et al.,2017).While G protein-mediated signalling is initiated upon GPCR stimulation,activated GPCRs return to their basal levels through a GRK-and arrestin-regulated desensitization process(Santos et al.,2017).In addition to modulating receptor desensitization,β-arrestin also regulates downstream events that are distinct from classical G protein signalling(Ahn et al.,2020).

关键词： stimulation return

Neutrophils are shaped by the tumor microenvironment:novel possibilities for targeting neutrophils in cancer

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1788-1790页

作者： Carlos Silvestre-Roig Lydia Kalafati Triantafyllos Chavakis institute of Experimental Pathology(ExPat) Center for Molecular Biology of Inflammation(ZMBE)University of MünsterMünsterGermany institute for clinical Chemistry and Laboratory Medicine University Hospital and Faculty of MedicineTechnische Universität DresdenDresdenGermany

In a recent paper published in Science,Ng et al.provide seminal insights into the process through which neutrophils are reprogrammed by the tumor environment,leading to a convergent transition from different neutrophil states towards a unique end-stage differentiated pro-tumor phenotype.1 These findings have major translational implications as they provide potential neutrophil-related targets for tumor immunotherapy.

关键词： al. neutrophils tumor

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 subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,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 irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(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 cells.Adoptive 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 cells.In 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

Comparison of clinical features and outcomes of proliferative,fibrotic,and mixed subtypes of IgG4-related disease:A retrospective cohort study

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Chinese Medical Journal 2024年第3期137卷 303-311页

作者： Linyi Peng Xinlu Zhang Jiaxin Zhou Jieqiong Li Zheng Liu Hui Lu Yu Peng Yunyun Fei Yan Zhao Xiaofeng Zeng Wen Zhang Department of Rheumatology and clinical immunology Peking Union Medical College HospitalNational Clinical Research Center for Dermatologic and Immunologic DiseasesState Key Laboratory of Complex Severe and Rare DiseasesThe Ministry of Education Key LaboratoryBeijing 100730China institute of clinical Medicine Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Background:Immunoglobulin G4-related disease(IgG4-RD)is a recently recognized immune-mediated disorder that can affect almost any organ in the human body.IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’clinicopathological characteristics.This study aimed to compare the clinical manifestations,laboratory findings,and treatment outcomes of IgG4-RD among different subtypes.Methods:We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021.The patients were divided into three groups according to their clinicopathological characteristics:proliferative,fibrotic,and mixed subtypes.We compared demographic features,clinical manifestations,organ involvement,laboratory tests,and treatment agents across three subtypes.We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants.Moreover,risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results:We classified the 622 patients into three groups consisting of 470 proliferative patients,55 fibrotic patients,and 97 mixed patients,respectively.We found that gender distribution,age,disease duration,and frequency of allergy history were significantly different among subgroups.In terms of organ involvement,submandibular and lacrimal glands were frequently involved in the proliferative subtype,while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype.The comparison of laboratory tests revealed that eosinophils(P=0.010),total IgE(P=0.006),high-sensitivity C-reactive protein(P<0.001),erythrocyte sedimentation rate(P<0.001),complement C4(P<0.001),IgG(P=0.001),IgG1(P<0.001),IgG4(P<0.001),and IgA(P<0.001),at baseline were significantly different among three subtypes.Compared with proliferative and mixed subtypes,the fibrotic subtype showed the lowest rate of relapse(log-rank P=0.014).Conclus

关键词： IgG4-related disease Proliferative subtype Fibrotic subtype clinical features Treatment outcome

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal Cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

Investigating the Mechanism of Qu Du Qiang Fei 1 Hao Fang Formula against Coronavirus Disease 2019 Based on Network Pharmacology Method

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 93-103页

作者： Yuan-Hua Wang He-Yang Zhou Jin-Yun Ma Gui-Qing Ding Hua Yu Yong-Sheng Jin Xiao-Dong Cheng institute of clinical immunology Yue-Yang Hospital of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina School of Pharmacy Naval Medical UniversityShanghaiChina

Objective:Qu Du Qiang Fei 1 Hao Fang(QDQF1)is a novel Chinese herbal medicine formula used to treat coronavirus disease 2019(COVID-19).However,the pharmacological mechanisms of action of QDQF1 remain unclear.The objective of this study was to identify the effective ingredients and biological targets of QDQF1 for COVID-19 treatment.Materials and Methods:The effective ingredients and mechanisms of action of QDQF1 were analyzed by using network pharmacology methods,which included an analysis of the effective ingredients and corresponding targets,COVID-19-related target acquisition,compound-target network analyses,protein-protein interaction network analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses,and molecular docking studies.Results:In total,288 effective QDQF1 ingredients were identified.We identified 51 core targets from the 148 targets through an overlap between putative QDQF1 targets and COVID-19-related targets.Six key components,including formononetin,kaempferol,luteolin,naringenin,quercetin,and wogonin were identified through component-target network analyses.GO functional enrichment analysis of the core targets revealed 1296 items,while KEGG pathway enrichment analysis identified 148 signaling pathways.Nine central targets(CCL2,CXCL8,IL1B,IL6,MAPK1,MAPK3,MAPK8,STAT3,and TNF)related to the COVID-19 pathway were identified in the KEGG pathway enrichment analysis.Furthermore,molecular docking analysis suggested that the docking scores of the six key components to the nine central targets were better than those to remdesivir.Conclusions:QDQF1 may regulate multiple immune-and inflammation-related targets to inhibit the progression of severe acute respiratory syndrome coronavirus 2,and thus,may be suitable for the treatment of COVID-19.

关键词： Coronavirus disease 2019 molecular docking molecular mechanism network pharmacology Qu Du Qiang Fei 1 Hao Fang formula

Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach

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Animal Models and Experimental Medicine 2024年第1期7卷 36-47页

作者： Roa'a H.S.Yosief Iqbal M.Lone Aharon Nachshon Heinz Himmelbauer Irit Gat-Viks Fuad A.Iraqi Department of clinical Microbiology and immunology Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael School of molecular Cell Biology and Biotechnology George S.Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael institute of Computational Biology Department of BiotechnologyUniversity of Natural Resources and Life SciencesMuthgasse 181190 ViennaAustria

Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.

关键词： aspergillus fumigatus infection collaborative cross(CC)mice gene expression profile gene-network host susceptibility quantitative trait loci(QTL)mapping RNA-Seq