European Journal of Immunology最新文献

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 : 2025-01-01 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":"e202451358"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","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}

引用次数: 0

Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC. 人类非淋巴组织 DC 的制备和流式细胞术分析指南。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI: 10.1002/eji.202250325

Diana Dudziak, Lukas Heger, William W Agace, Joyce Bakker, Tanja D de Gruijl, Regine J Dress, Charles-Antoine Dutertre, Thomas M Fenton, Marieke F Fransen, Florent Ginhoux, Oded Heyman, Yael Horev, Florian Hornsteiner, Vinitha Kandiah, Paz Kles, Ruth Lubin, Gabriel Mizraji, Anastasia Prokopi, Or Saar, Sieghart Sopper, Patrizia Stoitzner, Helen Strandt, Martina M Sykora, Elisa C Toffoli, Christoph H Tripp, Kim van Pul, Rieneke van de Ven, Asaf Wilensky, Simon Yona, Claudia Zelle-Rieser

{"title":"Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC.","authors":"Diana Dudziak, Lukas Heger, William W Agace, Joyce Bakker, Tanja D de Gruijl, Regine J Dress, Charles-Antoine Dutertre, Thomas M Fenton, Marieke F Fransen, Florent Ginhoux, Oded Heyman, Yael Horev, Florian Hornsteiner, Vinitha Kandiah, Paz Kles, Ruth Lubin, Gabriel Mizraji, Anastasia Prokopi, Or Saar, Sieghart Sopper, Patrizia Stoitzner, Helen Strandt, Martina M Sykora, Elisa C Toffoli, Christoph H Tripp, Kim van Pul, Rieneke van de Ven, Asaf Wilensky, Simon Yona, Claudia Zelle-Rieser","doi":"10.1002/eji.202250325","DOIUrl":"10.1002/eji.202250325","url":null,"abstract":"This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs, and various nonlymphoid tissues. Within this article, detailed protocols are presented that allow for the generation of single-cell suspensions from human nonlymphoid tissues including lung, skin, gingiva, intestine as well as from tumors and tumor-draining lymph nodes with a subsequent analysis of dendritic cells by flow cytometry. Further, prepared single-cell suspensions can be subjected to other applications including cellular enrichment procedures, RNA sequencing, functional assays, etc. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all co-authors, making it an essential resource for basic and clinical DC immunologists.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2250325"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816629","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

Decoding complement: Novel disease insights and therapeutic horizons. 解码补体：新的疾病认识和治疗前景。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-10-25 DOI: 10.1002/eji.202350905

Christian M Karsten, Jörg Köhl

引用次数: 0

Alveolar epithelial cells shape lipopolysaccharide-induced inflammatory responses and reprogramming of alveolar macrophages. 肺泡上皮细胞塑造脂多糖诱导的炎症反应和肺泡巨噬细胞的重编程。

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.202350378

Wei Jiang, Yeying Chen, Cheng-Yun Yu, Benkun Zou, Yimeng Lu, Qian Yang, Zihui Tang, Weiying Mao, Jing Li, Han Han, Lingyun Shao, Jiashun Zeng, Yiwei Chu, Jianguo Tang, Mingfang Lu

{"title":"Alveolar epithelial cells shape lipopolysaccharide-induced inflammatory responses and reprogramming of alveolar macrophages.","authors":"Wei Jiang, Yeying Chen, Cheng-Yun Yu, Benkun Zou, Yimeng Lu, Qian Yang, Zihui Tang, Weiying Mao, Jing Li, Han Han, Lingyun Shao, Jiashun Zeng, Yiwei Chu, Jianguo Tang, Mingfang Lu","doi":"10.1002/eji.202350378","DOIUrl":"10.1002/eji.202350378","url":null,"abstract":"Alveolar macrophages (AMs) are sentinels in the airways, where they sense and respond to invading microbes and other stimuli. Unlike macrophages in other locations, AMs can remain responsive to Gram-negative lipopolysaccharides (LPS) after they have responded to LPS in vivo (they do not develop \"endotoxin tolerance\"), suggesting that the alveolar microenvironment may influence their responses. Although alveolar epithelial cells (AECs) normally limit AMs' innate responses, preventing inflammation induced by harmless antigens in the lung, how AECs influence the innate responses of AMs to infectious agents has been uncertain. Here we report that (1) after exposure to aspirated (intranasal instillation) LPS, AMs increase their responses to TLR agonists and elevate their phagocytic and bactericidal activities in mice; (2) Aspirated LPS pre-exposure increases host resistance to pulmonary infection caused by Gram-negative bacteria and the protection effect lasts for at least 35 days; (3) LPS stimulation of AECs both increases AMs' innate immune responses and prevents AMs from developing tolerance in vitro; (4) Upon LPS stimulation, AMs secreted TNF-α induces AECs to release GM-CSF, which potentiates AMs' response. These experiments have revealed a previously unappreciated role that AECs may play in boosting the innate responses of AMs and promoting resistance to pulmonary infections.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2350378"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581373","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

Metabolic Reprogramming of Fibroblastic Reticular Cells in Immunity and Tolerance. 免疫和耐受中成纤维网细胞的代谢重编程

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1002/eji.202451321

Dejun Kong, Marina WillsonShirkey, Wenji Piao, Long Wu, Shunqun Luo, Allision Kensiski, Jing Zhao, Young Lee, Reza Abdi, Hong Zheng, Jonathan S Bromberg

{"title":"Metabolic Reprogramming of Fibroblastic Reticular Cells in Immunity and Tolerance.","authors":"Dejun Kong, Marina WillsonShirkey, Wenji Piao, Long Wu, Shunqun Luo, Allision Kensiski, Jing Zhao, Young Lee, Reza Abdi, Hong Zheng, Jonathan S Bromberg","doi":"10.1002/eji.202451321","DOIUrl":"10.1002/eji.202451321","url":null,"abstract":"Fibroblastic reticular cells (FRCs) are pivotal stromal components that maintain the structure of secondary lymphoid tissues and modulate the immune responses within the lymphoid microenvironment. In response to specific immune or inflammatory stimuli, such as infection or autoimmune triggers, FRCs undergo significant metabolic reprogramming. This process, originally characterized in cancer research, involves the regulation of key metabolic enzymes, pathways, and metabolites, resulting in functional transformations of these cells. Specifically, viruses stimulate FRCs to enhance the tricarboxylic acid cycle, while rheumatoid arthritis and sepsis prompt FRCs to increase oxidative phosphorylation. These changes enable FRCs to adapt their functions, such as proliferation or cytokine secretion, thereby effectively regulating the immune microenvironment to meet the dynamic needs of the immune system. This review provides a comprehensive update on the metabolic reprogramming of FRCs, highlighting how these changes support immune tolerance and response under varied physiological conditions.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451321"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646277","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 Cells With Complementary B Cell Receptors Can Kill Each Other. 具有互补 B 细胞受体的 B 细胞可以互相杀伤

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-09 DOI: 10.1002/eji.202350890

Ramakrishna Prabhu Gopalakrishnan, Marius Sigurdsson Østrøm, Frode Miltzow Skjeldal, Oddmund Bakke, Bjarne Bogen, Peter Csaba Huszthy

{"title":"B Cells With Complementary B Cell Receptors Can Kill Each Other.","authors":"Ramakrishna Prabhu Gopalakrishnan, Marius Sigurdsson Østrøm, Frode Miltzow Skjeldal, Oddmund Bakke, Bjarne Bogen, Peter Csaba Huszthy","doi":"10.1002/eji.202350890","DOIUrl":"10.1002/eji.202350890","url":null,"abstract":"B cells differentiate from hematopoietic stem cells in the bone marrow (BM) and migrate as transitional cells to the spleen where final maturation takes place. Due to the enormous diversity in variable (V) regions of B cell receptors for antigen (BCR), B cells with complementary BCRs are likely to be generated. These could encounter each other in the BM or in secondary lymphoid organs. The outcome of such an event is unknown. To study this issue, we used two strains of gene-modified mice whose B cells display complementary BCRs. B cells of one strain express an idiotype+ (Id+) BCR while B cells of the other strain display an anti-idiotypic (αId) BCR. In vitro, B cells with complementary BCRs killed each other in a mechanism that required physical binding between BCR V-regions. In contrast, killing was unilateral in vivo: αId B cells with a follicular (FO) B cell phenotype were expanded, while Id+ B cells with a marginal zone (MZ) phenotype became deleted. The results show that B cells with complementary BCRs can recognize and regulate each other in vivo. This mechanism should be taken into account in theories for idiotypic regulation of the immune system.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202350890"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613193","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

IL1R2 Acts as a Negative Regulator of Monocyte Recruitment During Inflammation. IL1R2在炎症过程中作为单核细胞募集的负调节因子。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1002/eji.202451468

Adeline Cros, Elodie Segura

引用次数: 0

Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions. 利用人工体内CDR3区域多样化技术探测TCR特异性。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1002/eji.202451434

Orlando B Giorgetti, Annette Haas-Assenbaum, Thomas Boehm

{"title":"Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions.","authors":"Orlando B Giorgetti, Annette Haas-Assenbaum, Thomas Boehm","doi":"10.1002/eji.202451434","DOIUrl":"10.1002/eji.202451434","url":null,"abstract":"The T-cell receptor sequences expressed on cells recognizing a specific peptide in the context of a given MHC molecule can be explored for common features that might explain their antigen specificity. However, despite the development of numerous experimental and bioinformatic strategies, the specificity problem remains unresolved. To address the need for additional experimental paradigms, we report here on an in vivo experimental strategy designed to artificially diversify a transgenic TCR by CRISPR/Cas9-mediated mutagenesis of Tcra and Tcrb chain genes. In this system, an initially monoclonal repertoire of known specificity is converted into an oligoclonal pool of TCRs of altered antigen reactivity. Tracking the fate of individual clonotypes during the intrathymic differentiation process illuminates the strong selective pressures that shape the repertoire of naïve T cells. Sequence analyses of the artificially diversified repertoires identify key amino acid residues in the CDR3 regions required for antigen recognition, indicating that artificial diversification of well-characterized TCR transgene sequences helps to reduce the complexities of learning the rules of antigen recognition.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451434"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764914","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

Memory Phenotype Tfh Cells Develop Without Overt Infection and Support Germinal Center Formation and B Cell Responses to Viral Infection. 记忆表型 Tfh 细胞在没有明显感染的情况下发育，支持生殖中心的形成和 B 细胞对病毒感染的反应。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-20 DOI: 10.1002/eji.202451291

Alistair L J Symonds, Zabreen Busharat, Mengmeng Du, Tizong Miao, Suling Li, Xiujuan Hou, Ping Wang

{"title":"Memory Phenotype Tfh Cells Develop Without Overt Infection and Support Germinal Center Formation and B Cell Responses to Viral Infection.","authors":"Alistair L J Symonds, Zabreen Busharat, Mengmeng Du, Tizong Miao, Suling Li, Xiujuan Hou, Ping Wang","doi":"10.1002/eji.202451291","DOIUrl":"10.1002/eji.202451291","url":null,"abstract":"Pathogen-induced memory Tfh cells are important to maintain high-affinity antibodies against pathogens. We have now discovered Tfh cells with a similar memory phenotype (MP) that develop in pathogen-free conditions. These MP Tfh cells are similar to pathogen-induced memory Tfh in both phenotype and function. They express FR4 and Egr2, which are both found in pathogen-induced memory Tfh cells. FR4+Egr2+ CD4 MP cells express genes involved in the development of Tfh cells and homeostatic proliferation, as well as key metabolic pathways discovered in pathogen-induced memory Tfh cells. MP Tfh cells can support B cell-mediated IgG production in vitro and induce germinal center formation and anti-viral antibodies in response to virus infection. These mouse MP Tfh cells share a similar phenotype to human circulating Tfh cells that are increased in Sjögren's syndrome patients. Although Foxp3-positive circulating T follicular regulatory (Tfr) cells are normal, a proportion of circulating Tfh cells from patients express increased levels of T-bet, which is associated with high levels of inflammatory pathology. Thus, although they do not require overt infection for their development, MP Tfh cells are important for protective immune responses, and dysregulated MP Tfh responses may play a role in autoimmunity.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e202451291"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680027","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 : 2025-01-01 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":"https://doi.org/10.1002/eji.202451386","url":null,"abstract":"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.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":"e202451386"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","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