European Journal of Immunology最新文献_第3页

TSLP and TSLPr Expression and Localization in the Airways of COPD and Non-COPD Patients. TSLP和TSLPr在COPD和非COPD患者气道中的表达和定位

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 DOI: 10.1002/eji.202451480

Lynda Saber Cherif, Maëva A Devilliers, Jeanne-Marie Perotin, Julien Ancel, Alexandre Vivien, Arnaud Bonnomet, Gonzague Delepine, Anne Durlach, Myriam Polette, Gaëtan Deslée, Valérian Dormoy

引用次数: 0

The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice. 微生物组改变穿孔素缺陷小鼠嗜血细胞淋巴组织细胞增多症的表现形式

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-16 DOI: 10.1002/eji.202451061

Jasmin Mann, Solveig Runge, Christoph Schell, Katja Gräwe, Gudrun Thoulass, Jessica Lao, Sandra Ammann, Sarah Grün, Christoph König, Sarah A Berger, Benedikt Hild, Peter Aichele, Stephan P Rosshart, Stephan Ehl

{"title":"The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice.","authors":"Jasmin Mann, Solveig Runge, Christoph Schell, Katja Gräwe, Gudrun Thoulass, Jessica Lao, Sandra Ammann, Sarah Grün, Christoph König, Sarah A Berger, Benedikt Hild, Peter Aichele, Stephan P Rosshart, Stephan Ehl","doi":"10.1002/eji.202451061","DOIUrl":"10.1002/eji.202451061","url":null,"abstract":"Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by inborn errors of cytotoxicity. Patients with biallelic PRF1 null mutations (encoding perforin) usually develop excessive immune cell activation, hypercytokinemia, and life-threatening immunopathology in the first 6 months of life, often without an apparent infectious trigger. In contrast, perforin-deficient (PKO) mice only develop HLH after systemic infection with lymphocytic choriomeningitis virus (LCMV). We hypothesized that restricted microbe-immune cell interactions due to specific pathogen-free (SPF) housing might explain the need for this specific viral trigger in PKO mice. To investigate the influence of a \"wild\" microbiome in PKO mice, we fostered PKO newborns with Wildling microbiota ('PKO-Wildlings') and monitored them for signs of HLH. PKO-Wildlings survived long-term without spontaneous disease. Also, systemic infection with vaccinia virus did not reach the threshold of immune activation required to trigger HLH in PKO-Wildlings. Interestingly, after infection with LCMV, PKO-Wildlings developed an altered HLH pattern. This included lower IFN-γ serum levels along with improved IFN-γ-driven anemia, but more elevated levels of IL-17 and increased liver inflammation compared with PKO-SPF mice. Thus, wild microbiota alone is not sufficient to trigger HLH in PKO mice, but host-microbe interactions shape inflammatory cytokine patterns, thereby influencing manifestations of HLH immunopathology.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451061"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer. I 型干扰素驱动一种对 TCR 刺激惰性的细胞状态，并可能阻碍癌症中 T 细胞的有效分化。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-12 DOI: 10.1002/eji.202451371

Dillon Corvino, Martin Batstone, Brett G M Hughes, Tim Kempchen, Susanna S Ng, Nazhifah Salim, Franziska Schneppenheim, Denise Rommel, Ananthi Kumar, Sally Pearson, Jason Madore, Lambross T Koufariotis, Lisa Maria Steinheuer, Dilan Pathirana, Kevin Thurley, Michael Hölzel, Nicholas Borcherding, Matthias Braun, Tobias Bald

{"title":"Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer.","authors":"Dillon Corvino, Martin Batstone, Brett G M Hughes, Tim Kempchen, Susanna S Ng, Nazhifah Salim, Franziska Schneppenheim, Denise Rommel, Ananthi Kumar, Sally Pearson, Jason Madore, Lambross T Koufariotis, Lisa Maria Steinheuer, Dilan Pathirana, Kevin Thurley, Michael Hölzel, Nicholas Borcherding, Matthias Braun, Tobias Bald","doi":"10.1002/eji.202451371","DOIUrl":"10.1002/eji.202451371","url":null,"abstract":"Background: Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV-positive and HPV-negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent/metastatic HNSCC, response variability persists regardless of HPV status. This study aimed to explore the CD8+ T-cell landscape in HPV-negative HNSCC.Methods: We performed simultaneous single-cell RNA and TCR sequencing of CD8+ tumor-infiltrating lymphocytes (TILs) from treatment-naïve HPV-negative HNSCC patients. Additionally, cells were stimulated ex vivo, which allowed for the tracking of clonal transcriptomic responses.Results: Our analysis identified a subset of CD8+ TILs highly enriched for interferon-stimulated genes (ISG). TCR analysis revealed ISG cells are clonally related to a population of granzyme K (GZMK)-expressing cells. However, unlike GZMK cells, which exhibited rapid effector-like phenotypes following stimulation, ISG cells were transcriptionally inert. Additionally, ISG cells showed specific enrichment within tumor and were found across multiple tumor entities.Conclusions: ISG-enriched CD8+ TILs are a consistent feature of various tumor entities. These cells are poorly understood but possess characteristics that may impact antitumor immunity. Understanding the unique properties and functionality of ISG cells could offer innovative treatment approaches to improve patient outcomes in HPV-negative HNSCC and other cancer types.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451371"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Anti-Human P2X7 Monoclonal Antibody (Clone L4) Can Mediate Complement-Dependent Cytotoxicity of Human Leukocytes.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 DOI: 10.1002/eji.202451196

Amal Elhage, Debbie Watson, Ronald Sluyter

{"title":"The Anti-Human P2X7 Monoclonal Antibody (Clone L4) Can Mediate Complement-Dependent Cytotoxicity of Human Leukocytes.","authors":"Amal Elhage, Debbie Watson, Ronald Sluyter","doi":"10.1002/eji.202451196","DOIUrl":"10.1002/eji.202451196","url":null,"abstract":"P2X7 is an extracellular adenosine 5'-triphosphate (ATP)-gated cation channel that plays various roles in inflammation and immunity. P2X7 is present on peripheral blood monocytes, dendritic cells (DCs), and innate and adaptive lymphocytes. The anti-human P2X7 monoclonal antibody (mAb; clone L4), used for immunolabelling P2X7 or blocking P2X7 activity, is a murine IgG2b antibody, but its ability to mediate complement-dependent cytotoxicity (CDC) is unknown. In this study the functionality of this mAb was confirmed by inhibition of ATP-induced Ca2+ responses in HEK-293 cells expressing P2X7 (HEK-P2X7). Spectrophotometric measurements of lactate dehydrogenase release demonstrated that the anti-P2X7 mAb mediated CDC in HEK-P2X7 but not HEK-293 cells. Further, flow cytometric measurements of the viability dye, 7-aminoactinomycin D, showed that this mAb mediated CDC in human RPMI 8226 but not mouse J774 cells. Immunolabelling with this mAb and flow cytometry revealed that relative amounts of cell surface P2X7 varied between human peripheral blood leukocytes. As such, the anti-P2X7 mAb preferentially mediated CDC of leukocytes that displayed relatively high cell surface P2X7, namely monocytes, DCs, natural killer T cells, myeloid-derived suppressor cells, and T helper 17 cells. Together, this data highlights a novel approach to target cellular P2X7 and to limit unwanted P2X7 functions.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":"e202451196"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Direct Inhibitory Effect of HTLV-1-Infected T Cells on the Production of Anti-Ro/SS-A Antibody by B Cells from Patients with Sjögren's Syndrome. htlv -1感染T细胞对Sjögren综合征患者B细胞产生抗ro /SS-A抗体的直接抑制作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 DOI: 10.1002/eji.202451279

Kinya Nagata, Masako Tsukamoto, Yosuke Nagasawa, Noboru Kitamura, Hideki Nakamura

{"title":"Direct Inhibitory Effect of HTLV-1-Infected T Cells on the Production of Anti-Ro/SS-A Antibody by B Cells from Patients with Sjögren's Syndrome.","authors":"Kinya Nagata, Masako Tsukamoto, Yosuke Nagasawa, Noboru Kitamura, Hideki Nakamura","doi":"10.1002/eji.202451279","DOIUrl":"https://doi.org/10.1002/eji.202451279","url":null,"abstract":"The reasons for the low frequency of anti-Ro/SS-A antibody in patients with HTLV-1-associated myelopathy complicated with Sjögren's syndrome (SS) are unclear. In this study, we investigated whether HTLV-1-infected T cells can act directly on B cells and suppress B cells' production of antibodies, including anti-Ro/SS-A antibody. For this purpose, we established an in vitro T-cell-free B-cell antibody production system. The productions of total IgG and anti-cytomegalovirus IgG in B cells from healthy subjects and those of total IgG and anti-Ro/SS-A IgG in B cells from SS patients were significantly suppressed by the addition of HTLV-1-positive T-cell lines (MT-2 and HCT-5). Our analysis of co-cultured B cells identified no sign of HTLV-1 infection and revealed that MT-2 and HCT-5 cells act on the early stages of B-cell differentiation, not the activation stage. MT-2 and HCT-5 cells constitutively expressed CD70, ICAM-1, LAP (TGF-β), and PD-L1/2, but blocking monoclonal antibodies to these molecules or PD-L1/2 receptor PD-1 had no significant canceling effect on B-cell IgG production regarding their suppressive activity. Importantly, autologous CD4+CD25+CD127low Treg cells had no inhibitory effect on B-cell IgG production. These results demonstrate that HTLV-1-positive T cells can directly suppress B-cell antibody production through mechanisms that differ from Treg functions.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":"e202451279"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ubiquitin-Conjugating Enzyme Ubc13 in Macrophages Suppresses Lung Tumor Progression Through Inhibiting PD-L1 Expression. 巨噬细胞中泛素偶联酶Ubc13通过抑制PD-L1表达抑制肺癌进展

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-23 DOI: 10.1002/eji.202451118

Siying Sun, Jun Ni, Jiamin Liu, Juofang Tan, Runsen Jin, Hecheng Li, Xuefeng Wu

{"title":"Ubiquitin-Conjugating Enzyme Ubc13 in Macrophages Suppresses Lung Tumor Progression Through Inhibiting PD-L1 Expression.","authors":"Siying Sun, Jun Ni, Jiamin Liu, Juofang Tan, Runsen Jin, Hecheng Li, Xuefeng Wu","doi":"10.1002/eji.202451118","DOIUrl":"https://doi.org/10.1002/eji.202451118","url":null,"abstract":"Tumor cell-intrinsic ubiquitin-conjugating enzyme Ubc13 promotes tumorigenesis, yet how Ubc13 in immune cell compartments regulates tumor progression remains elusive. Here, we show that myeloid-specific deletion of Ubc13 (Ubc13fl/flLyz2Cre) leads to accelerated transplanted lung tumor growth in mice. Compared with their littermate controls, tumor-bearing Ubc13fl/flLyz2Cre mice had lower proliferation and effector function of CD8+ T lymphocytes, accompanied by increased infiltration of myeloid-derived suppressor cells within the tumor microenvironment. Mechanistically, Ubc13 deficiency leads to upregulation of Arg1 and PD-L1, the latter is modulated by reduced Ubc13-mediated K63-linked polyubiquitination and increasing activation of Akt, thereby inducing skewness to protumoral polarization and immunosuppressive manifestation. Taken together, we reveal that macrophage-intrinsic Ubc13 restrains lung tumor progression, indicating that activating Ubc13 in macrophages could be an effective immunotherapeutic regimen for lung cancer.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451118"},"PeriodicalIF":4.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

B Cell Receptor Repertoire Analysis of the CD21^lo B Cell Compartment in Healthy Individuals, Patients With Sjögren's Disease, and Patients With Radiographic Axial Spondyloarthritis. 健康个体、Sjögren病患者和x线轴性脊柱炎患者CD21lo B细胞区室的B细胞受体库分析

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-20 DOI: 10.1002/eji.202451398

Rick Wilbrink, Linda van der Weele, Anneke J P L Spoorenberg, Niek de Vries, Ilse T G Niewold, Gwenny M Verstappen, Frans G M Kroese

{"title":"B Cell Receptor Repertoire Analysis of the CD21lo B Cell Compartment in Healthy Individuals, Patients With Sjögren's Disease, and Patients With Radiographic Axial Spondyloarthritis.","authors":"Rick Wilbrink, Linda van der Weele, Anneke J P L Spoorenberg, Niek de Vries, Ilse T G Niewold, Gwenny M Verstappen, Frans G M Kroese","doi":"10.1002/eji.202451398","DOIUrl":"https://doi.org/10.1002/eji.202451398","url":null,"abstract":"B cells with low or absent expression of CD21 (CD21lo B cells) gained attention due to their expansion in the peripheral blood of patients with immune-mediated, rheumatic diseases. This is not only observed in typical autoimmune diseases like systemic lupus erythematosus and Sjögren's disease (SjD) but also in radiographic axial spondyloarthritis (r-axSpA), which is considered an autoinflammatory disease. To gain more insight into the origins of the heterogeneous CD21lo B-cell population, and its relation to the plasmablast (PB) compartment, we profiled the B-cell-receptor (BCR) repertoire in CD27- and CD27+ fractions of CD21lo B cells and early PBs using next-generation sequencing. Populations were sorted from peripheral blood of healthy individuals, SjD patients, and r-axSpA patients (n = 10 for each group). In healthy individuals and both patient groups, our findings indicate that CD27-CD21lo B cells, which exhibit few mutations in their BCR, may develop into CD27+CD21lo B cells and PBs, both marked by considerably more mutations. Given the known expansion of circulating CD27-CD21lo B cells in SjD and r-axSpA patients and clonal relationships with both CD27+CD21lo B cells and early PBs, these cells might actively contribute to (pathological) immune responses in rheumatic diseases with autoimmune and/or autoinflammatory characteristics.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451398"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Half-Life Extension of the IgG-Degrading Enzyme (IdeS) Using Fc-Fusion Technology. 利用fc融合技术延长igg降解酶（IdeS）半衰期。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-20 DOI: 10.1002/eji.202451264

Victoria Daventure, Melissa Bou-Jaoudeh, Emna Hannachi, Alejandra Reyes-Ruiz, Amélia Trecco, Sandrine Delignat, Sébastien Lacroix-Desmazes, Claire Deligne

{"title":"Half-Life Extension of the IgG-Degrading Enzyme (IdeS) Using Fc-Fusion Technology.","authors":"Victoria Daventure, Melissa Bou-Jaoudeh, Emna Hannachi, Alejandra Reyes-Ruiz, Amélia Trecco, Sandrine Delignat, Sébastien Lacroix-Desmazes, Claire Deligne","doi":"10.1002/eji.202451264","DOIUrl":"https://doi.org/10.1002/eji.202451264","url":null,"abstract":"Imlifidase (IdeS) is a bacterial protease that hydrolyzes human IgG in their hinge region, decreasing their half-life and abrogating their Fc-mediated properties. It is now successfully used in therapy to prevent graft rejection during kidney transplants and is being clinically evaluated in several IgG-mediated autoimmune diseases. IdeS short half-life however limits its clinical use, particularly in the case of chronic diseases that would request repeated administrations. Here, we developed IdeS-Fc fusion proteins as a divalent homodimer (IdeS-Fcdiv) or a monovalent heterodimer (IdeS-Fcmonov), in order to extend the IgG-depleting action of IdeS over time. Both IdeS-Fc efficiently separated monoclonal and polyclonal human IgG into F(ab')2 and Fc fragments, although with slower kinetics than their native counterpart. IdeS-Fcmonov exhibited a seven-fold half-life extension in vivo as compared with IdeS, and a significantly better residual cleavage of human IgG at later time points after injection. Our results provide proof of concept for the use of an IdeS with extended IgG-hydrolyzing functions in vivo that could rapidly translate to the clinic.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451264"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Efficiency of Brain-Derived Neurotrophic Factor Secretion by mRNA-Electroporated Regulatory T Cells Is Highly Impacted by Their Activation Status. mRNA导入的调节性T细胞分泌脑源性神经营养因子的效率受其活化状态的影响很大。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-19 DOI: 10.1002/eji.202451005

Jasper Van den Bos, Ibo Janssens, Morgane Vermeulen, Amber Dams, Hans De Reu, Stefanie Peeters, Carole Faghel, Yousra El Ouaamari, Inez Wens, Nathalie Cools

{"title":"The Efficiency of Brain-Derived Neurotrophic Factor Secretion by mRNA-Electroporated Regulatory T Cells Is Highly Impacted by Their Activation Status.","authors":"Jasper Van den Bos, Ibo Janssens, Morgane Vermeulen, Amber Dams, Hans De Reu, Stefanie Peeters, Carole Faghel, Yousra El Ouaamari, Inez Wens, Nathalie Cools","doi":"10.1002/eji.202451005","DOIUrl":"https://doi.org/10.1002/eji.202451005","url":null,"abstract":"Genetic engineering of regulatory T cells (Tregs) presents a promising avenue for advancing immunotherapeutic strategies, particularly in autoimmune diseases and transplantation. This study explores the modification of Tregs via mRNA electroporation, investigating the influence of T-cell activation status on transfection efficiency, phenotype, and functionality. For this CD45RA+ Tregs were isolated, expanded, and modified to overexpress brain-derived neurotrophic factor (BDNF). Kinetics of BDNF expression and secretion were explored. Treg activation state was assessed by checking the expression of activation markers CD69, CD71, and CD137. Our findings show that only activated Tregs secrete BDNF post-genetic engineering, even though both activated and resting Tregs express BDNF intracellularly. Notably, the mTOR pathway and CD137 are implicated in the regulation of protein secretion in activated Tregs, indicating a complex interplay of signalling pathways. This study contributes to understanding the mechanisms governing protein expression and secretion in engineered Tregs, offering insights for optimizing cell-based therapies and advancing immune regulation strategies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451005"},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BAFF Blockade Attenuates B Cell MALT Formation in Conditional Nlrc5-Deficient Mice With Helicobacter felis Infection. BAFF阻断可减少感染幽门螺杆菌的nlrc5缺陷小鼠B细胞MALT的形成。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-12-17 DOI: 10.1002/eji.202451355

Dongmei Tong, Yuqi He, Shambel Araya Haile, Zoe Lee, Lena H M Le, Jack Emery, Georgie Wray-McCan, Michelle Chonwerawong, Dana J Philpott, Paul J Hertzog, Pascal Schneider, Richard L Ferrero, Le Ying

{"title":"BAFF Blockade Attenuates B Cell MALT Formation in Conditional Nlrc5-Deficient Mice With Helicobacter felis Infection.","authors":"Dongmei Tong, Yuqi He, Shambel Araya Haile, Zoe Lee, Lena H M Le, Jack Emery, Georgie Wray-McCan, Michelle Chonwerawong, Dana J Philpott, Paul J Hertzog, Pascal Schneider, Richard L Ferrero, Le Ying","doi":"10.1002/eji.202451355","DOIUrl":"https://doi.org/10.1002/eji.202451355","url":null,"abstract":"Helicobacter infection is a key cause of gastric B cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study examined the role of B cell-activating factor (BAFF), a major driver of B cell proliferation and many B cell disorders, in this malignancy using a model in which conditional knockout mice for NOD-like receptor family CARD domain-containing 5 (Nlrc5) are infected with Helicobacter felis. Gastric BAFF production was significantly increased in H. felis-infected Nlrc5mø-KO mice compared to wild-type. Blocking BAFF signalling, before or after the onset of Helicobacter-induced gastritis, significantly reduced MALT development, with fewer gastric B cell follicles and reduced gland hyperplasia. BAFF blockade also reshaped the immune cell landscape in the stomach, resulting in fewer CD4+ T cells, Tregs, macrophages and dendritic cells. Using a cell culture model, we identified the protein-coding BAFF transcripts that are upregulated in NLRC5-deficient macrophages stimulated with either H. felis or the NLRC5 agonist, lipopolysaccharide. Among the upregulated variants, TNFSF13B (BAFF)-206 acts as a transcription factor and is reported to enhance BAFF production in autoimmune diseases and cancer. Altogether, these findings implicate the NLRC5-BAFF signalling axis in Helicobacter-induced B cell MALT lymphoma, highlighting BAFF inhibition as a potential therapeutic approach.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451355"},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0