European Journal of Immunology最新文献_第3页

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 : 2025-01-24 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":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-24","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

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-16 DOI: 10.1002/eji.202451386

Michelle Broekhuizen, Marie-Louise van der Hoorn, Disha Vadgama, Michael Eikmans, Bojou J. Neecke, Johannes J. Duvekot, Pieter Fraaij, Irwin K. M. Reiss, Dana A. M. Mustafa, Lotte E. van der Meeren, Sam Schoenmakers

{"title":"Similar Spatial Expression of Immune-Related Proteins in SARS-CoV-2 Placentitis and Chronic Histiocytic Intervillositis","authors":"Michelle Broekhuizen, Marie-Louise van der Hoorn, Disha Vadgama, Michael Eikmans, Bojou J. Neecke, Johannes J. Duvekot, Pieter Fraaij, Irwin K. M. Reiss, Dana A. M. Mustafa, Lotte E. van der Meeren, Sam Schoenmakers","doi":"10.1002/eji.202451386","DOIUrl":"10.1002/eji.202451386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the placenta can lead to fetal distress and demise, characterized by severe trophoblast necrosis, chronic histiocytic intervillositis (CHI), and massive perivillous fibrin deposition. We aimed to uncover spatial immune-related protein changes in SARS-CoV-2 placentitis compared with CHI placentas and uncomplicated pregnancies to gain insight into the underlying pathophysiological mechanisms. Placentas were retrospectively collected from cases with SARS-CoV-2 placentitis resulting in fetal distress/demise (n = 9), CHI (n = 9), and uncomplicated term controls (n = 9). The expression of 53 immune-related proteins was quantified using GeoMx Digital Spatial Profiler in three separate compartments: villi (fetal compartment), intervillous space, and decidua (both maternal compartments). Compared with controls, SARS-CoV-2 placentitis and CHI both displayed differentially expressed proteins in the intervillous space only, including upregulation of myeloid markers (e.g., CD40, CD11c, CD68, CD163). Specifically, SARS-CoV-2 placentitis was associated with reduced expression of multiple apoptotic proteins (e.g., BAD, BIM, BLXL, BCL6). In conclusion, SARS-CoV-2 placentitis and CHI are associated with enhanced myeloid cell infiltration into the intervillous space, but not in the decidua and villi. The more prominently reduced apoptosis-related protein expression in SARS-CoV-2 placentitis may lead to an exaggerated immune response, causing acute placental dysfunction and fetal demise.\u0000 </section>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996980","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

Increased Phosphorylation of Intracellular Signaling Molecules Indicates Continuous Activation of Human Autoreactive B-Cells 细胞内信号分子磷酸化的增加表明人类自身反应性b细胞的持续激活。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-16 DOI: 10.1002/eji.202451361

Sanne Kroos, Nienke J. Blomberg, Joanneke C. Kwekkeboom, Rudi W. Hendriks, Odilia B. J. Corneth, René E. M. Toes, Hans U. Scherer

{"title":"Increased Phosphorylation of Intracellular Signaling Molecules Indicates Continuous Activation of Human Autoreactive B-Cells","authors":"Sanne Kroos, Nienke J. Blomberg, Joanneke C. Kwekkeboom, Rudi W. Hendriks, Odilia B. J. Corneth, René E. M. Toes, Hans U. Scherer","doi":"10.1002/eji.202451361","DOIUrl":"10.1002/eji.202451361","url":null,"abstract":"Many human autoimmune diseases (AIDs) are hallmarked by the presence and persistence of autoreactive B-cells. While autoreactive B-cells may frequently encounter antigens, the signals required to balance and maintain their activation and survival are mostly unknown. Understanding such signals may be important for strategies aimed at eliminating human B-cell autoreactivity. Here, we assessed intracellular signaling pathways in B cells targeting citrullinated protein antigens isolated from patients with rheumatoid arthritis (RA), a common and well-characterized AID. Peripheral blood mononuclear cells of 15 RA patients positive for anti-citrullinated protein antibodies (ACPA) were analyzed directly ex vivo using spectral flow cytometry and B-cell differentiation markers, citrullinated antigen-biotin-streptavidin tetramers, and intracellular (phosphoflow) markers. Tetanus toxoid (TT)-specific B cells served as antigen-specific comparators. In absence of any in vitro BCR stimulation, ACPA-expressing memory B cells (MBCs) displayed enhanced expression of Ki-67 and increased SYK-, BTK-, AKT-, and S6-phosphorylation compared with TT-specific MBCs. We demonstrate the simultaneous detection of B cell antigen-specificity and intracellular protein phosphorylation on the single-cell level. The data reveal that autoreactive B-cells in RA, in contrast to B cells against recall antigens, display enhanced phosphorylation of signaling molecules that point toward continuous, presumably antigen-mediated activation of the autoreactive B-cell compartment.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996975","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

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 : 2025-01-16 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

Survival of Human Bone Marrow Plasma Cells In Vitro Depends on the Support of the Stromal Cells, PI3K, and Canonical NF-kappaB Signaling 人骨髓浆细胞的体外存活依赖于基质细胞、PI3K和NF-kappaB信号的支持。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-08 DOI: 10.1002/eji.202451358

Zehra Uyar-Aydin, Shirin Kadler, Roland Lauster, Sina Bartfeld, Mark Rosowski

{"title":"Survival of Human Bone Marrow Plasma Cells In Vitro Depends on the Support of the Stromal Cells, PI3K, and Canonical NF-kappaB Signaling","authors":"Zehra Uyar-Aydin, Shirin Kadler, Roland Lauster, Sina Bartfeld, Mark Rosowski","doi":"10.1002/eji.202451358","DOIUrl":"10.1002/eji.202451358","url":null,"abstract":"Contrary to short-lived plasma cells, which survive only 3–5 days, long-lived plasma cells (LLPCs) contribute to the humoral memory of the body and thus also to many antibody-related diseases. The ability of plasma cells to persist over months, years, and even a lifetime has been demonstrated in vivo. Yet, the in vitro culture of human primary bone marrow-derived plasma cells has been limited to a few days. Here, we establish culture conditions for human primary bone marrow-derived plasma cells for 21 days. Plasma cells and stromal cells are isolated from human bone marrow and cultured in 2D or a 3D ceramic scaffold. The plasma cells’ survival and antibody secretion depend on direct contact with stromal cells. The culture promotes CD19-negative PCs. Inhibition of the PI3K or NF-kappaB pathways using chemical inhibitors reduced the survival of the plasma cells. These results underline the supportive role of the stromal cells for the survival of the LLPC and confirm mechanisms that were identified in mouse LLPCs also for human LLPCs. The culture described here will promote further studies to deepen our understanding of the human LLPC.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941729","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}

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Cover Story: Eur. J. Immunol. 1'25

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-08 DOI: 10.1002/eji.202570011

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Issue Information: Eur. J. Immunol. 1'25

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-08 DOI: 10.1002/eji.202570012

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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 : 2025-01-08 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":"10.1002/eji.202451279","url":null,"abstract":"<div>\u0000 \u0000 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.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","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}

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2024 German Society for Immunology Prizes.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-05 DOI: 10.1002/eji.202451593

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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":"10.1002/eji.202451118","url":null,"abstract":"<div>\u0000 \u0000 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.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"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