European Journal of Immunology最新文献_第2页

B-Cell Differentiation of Human Hematopoietic Progenitors Is Efficiently Supported by Wharton Jelly-Derived Mesenchymal Stem Cells 华顿胶源间充质干细胞有效支持人造血祖细胞b细胞分化。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-04 DOI: 10.1002/eji.70186

Louison Collet, Hakim Ouled-Haddou, Hussein Ghamlouch, Walaa Darwiche, Cathy Gomila, Brigitte Gubler, Loïc Garcon, Delphine Lebon, Jean-Pierre Marolleau

{"title":"B-Cell Differentiation of Human Hematopoietic Progenitors Is Efficiently Supported by Wharton Jelly-Derived Mesenchymal Stem Cells","authors":"Louison Collet, Hakim Ouled-Haddou, Hussein Ghamlouch, Walaa Darwiche, Cathy Gomila, Brigitte Gubler, Loïc Garcon, Delphine Lebon, Jean-Pierre Marolleau","doi":"10.1002/eji.70186","DOIUrl":"10.1002/eji.70186","url":null,"abstract":"Mesenchymal stem cells (MSC) represent the main stromal component of the bone marrow (BM) niche and are crucial to maintain hematopoietic tissue homeostasis. MSC exhibits extraordinary and multiple properties. In terms of expanding potential and differentiation capacity, Wharton jelly MSC (WJ-MSC), derived from the umbilical cord, was described as being greater and more performing than MSC from BM or other sources. WJ-MSC mimics the hematopoietic niche and supports hematopoietic stem cells (HSC) expansion ex vivo. This study aimed to evaluate the effects of human WJ-MSC cocultured with HSC in a B-cell differentiation protocol. Remarkably, results highlight WJ-MSC use as a preferable feeder layer to efficiently support HSC commitment toward the B-lineage. Over 11 days of HSC coculture with WJ-MSC, B-cell genes (E2A, RAG1, RAG2, etc.) expression patterns and B-cell markers (CD19, immunoglobulin chain, etc.) acquisition were evidenced. WJ-MSc were also able to unlock the B-lineage differentiation blockade of the acute lymphoblastic leukemia cell line Nalm16. This model might provide a new strategy to support ex vivo B-cell differentiation using the powerful properties of WJ-MSC. This study implements a new approach to improve understanding of B-leukemogenesis and B-cell acute lymphoblastic leukemia (B-ALL) pathophysiology.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615520","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

Nicotine Suppresses Human Memory Th Cell Subsets With Preferential Effects on Central Memory Th Cells in an α7 Nicotinic Acetylcholine Receptor-Dependent Manner α - 7烟碱乙酰胆碱受体依赖方式抑制人记忆Th细胞亚群及对中枢记忆Th细胞的优先作用

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-02 DOI: 10.1002/eji.70177

Fatemeh Gholizadeh, Mehri Hajiaghayi, Niloufar Rahbari, Jennifer S. Choi, Samantha Heidt, Alexia Como, Maryam Kazerouni, Melika Kargar, Aude Pinard-LaRoche, Steve C. C. Shih, Peter J. Darlington

{"title":"Nicotine Suppresses Human Memory Th Cell Subsets With Preferential Effects on Central Memory Th Cells in an α7 Nicotinic Acetylcholine Receptor-Dependent Manner","authors":"Fatemeh Gholizadeh, Mehri Hajiaghayi, Niloufar Rahbari, Jennifer S. Choi, Samantha Heidt, Alexia Como, Maryam Kazerouni, Melika Kargar, Aude Pinard-LaRoche, Steve C. C. Shih, Peter J. Darlington","doi":"10.1002/eji.70177","DOIUrl":"10.1002/eji.70177","url":null,"abstract":"Memory T helper (Th) cells sustain protective recall responses but can also drive chronic inflammation, necessitating precise regulation of their effector programs. Although Th cells produce acetylcholine (ACh) and express nicotinic acetylcholine receptors (nAChRs), the contribution of nAChRs to human memory Th function across central (Tcm) and effector (Tem) subsets is poorly defined. We examined the effect of nicotine and GTS-21, a compound previously described as targeting α7nAChR, on total memory Th cells and purified Tcm and Tem from healthy participants. Nicotine or GTS-21 diminished IFN-γ, IL-4, and IL-17A secretion, downregulated TBX21, GATA3, and RORC, and reduced NF-κB p65 phosphorylation in total memory Th cells. Disruption of CHRNA7 abolished nicotine-mediated suppression but did not eliminate the inhibitory effects of GTS-21. Within CCR7-defined subsets, nicotine and GTS-21 lowered Th1/Th2/Th17 frequencies in Tcm, but not in Tem. In purified subsets, nicotine suppressed IFN-γ, IL-4, IL-17A, IL-21, BCL6, and CD40L selectively in Tcm, whereas GTS-21 suppressed them in both Tcm and Tem. Collectively, nicotine engages an α7nAChR-dependent checkpoint that preferentially regulates Tcm responses, while GTS-21 exerts broader suppressive effects not fully explained by α7nAChR loss. This cholinergic checkpoint in Tcm may limit Tfh-associated help and pathogenic recall responses in immune-mediated disease.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13047356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607557","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

Multi-Parameter Spectral Flow Cytometry Panel for Immune Phenotyping of Murine B and T Cell Responses 小鼠B细胞和T细胞应答免疫表型的多参数谱流式细胞术面板。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-02 DOI: 10.1002/eji.70182

Kassandra Hoetzel, Hendrik Feuerstein, Julia Ludwig, Hedda Wardemann

引用次数: 0

Structure-Guided Engineering of TIGIT to Modulate Its Interaction With Nectin-4, a Tumour-Specific Antigen for the Development of Therapeutic Strategy 以结构为导向的TIGIT工程，调节其与肿瘤特异性抗原Nectin-4的相互作用，以制定治疗策略。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-02 DOI: 10.1002/eji.70179

Namrata Ganguli, Sayantan Shaw, Sohini Sarkar, Saumyadeep Goswami, Gayatri Mukherjee, Dibyendu Samanta

{"title":"Structure-Guided Engineering of TIGIT to Modulate Its Interaction With Nectin-4, a Tumour-Specific Antigen for the Development of Therapeutic Strategy","authors":"Namrata Ganguli, Sayantan Shaw, Sohini Sarkar, Saumyadeep Goswami, Gayatri Mukherjee, Dibyendu Samanta","doi":"10.1002/eji.70179","DOIUrl":"10.1002/eji.70179","url":null,"abstract":"<div>\u0000 \u0000 Nectin and nectin-like proteins are cell adhesion molecules belonging to the immunoglobulin superfamily that also play a crucial role in the process of immune modulation by interacting with immune receptors like TIGIT, DNAM-1, CD96 and PVRIG. Nectin-4 is a tumour-specific antigen that interacts exclusively with the inhibitory immune receptor TIGIT, resulting in inhibition of NK-cell cytotoxicity and facilitating the process of immune evasion by the cancer cells in the tumour microenvironment. Therefore, deciphering the molecular and structural mechanisms underlying this novel interaction can provide insights for the development of targeted immunotherapeutic interventions. In this study, using structure-guided mutagenesis studies, a novel TIGIT mutant is engineered exhibiting enhanced interaction affinity towards nectin-4 and reduced binding to other TIGIT ligands, such as PVR and nectin-2, which, in contrast to nectin-4, are predominantly expressed on healthy cells. Surface plasmon resonance-based biophysical studies were done to characterize and compare the interaction kinetics of the wild-type (WT) and the engineered mutant TIGIT ectodomains with their ligands. We have shown how a single point mutation of an amino acid residue located in the centre of the F strand of TIGIT dictates its interaction affinity with its ligand. These findings can provide a framework for the development of small-sized non-antibody therapeutics specifically targeted towards nectin-4 overexpressing cancer cells with minimal off-target effects on healthy cells.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607547","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

Human Blood IgA⁺ Memory B Cells Differ From IgG⁺ B Cells by Expressing Gut-Homing and Regulatory Markers. 人血液IgA+记忆B细胞与IgG+ B细胞通过表达肠道归巢和调节标记而不同。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-01 DOI: 10.1002/eji.70191

Louise Le Gal, Léo Boussamet, Alexandra Garcia, Jérémy Morille, Emilie Dugast, Arnaud B Nicot, David-Axel Laplaud, Laureline Berthelot

{"title":"Human Blood IgA+ Memory B Cells Differ From IgG+ B Cells by Expressing Gut-Homing and Regulatory Markers.","authors":"Louise Le Gal, Léo Boussamet, Alexandra Garcia, Jérémy Morille, Emilie Dugast, Arnaud B Nicot, David-Axel Laplaud, Laureline Berthelot","doi":"10.1002/eji.70191","DOIUrl":"https://doi.org/10.1002/eji.70191","url":null,"abstract":"IgA is the most produced immunoglobulin by the human body, mainly in secretions, and it exerts an important role in the activation and regulation of the immune system. Despite its importance, the phenotype of circulating IgA+ B cells is poorly described. Here, we deeply explored the phenotype of IgA+ memory B cells compared with IgG+ memory B cells from healthy donors using spectral flow cytometry. A bulk transcriptomic analysis was performed on isolated IgA+, IgG+ and IgM+ memory B cells. IgA2+ memory B cells expressed more gut-homing markers (CCR9, CCR10, integrin α4β7) and CD11b, GPR183, whereas IgG+ B cells expressed more CXCR3 and VLA4 at the protein level. Three other markers were discriminant: CD43 and PD-L1 were more expressed by IgA+ B cells, and CD25 associated with IgG+ B cells. The transcriptomic analysis of circulating IgA+, IgG+ and IgM+ memory B cells showed a particular signature of IgA+ B cells close to IgG+ B cells and highly different from IgM+ B cells. The transcription factor RUNX2 was upregulated in IgA+ B cells at the mRNA and protein level. Overall, we showed that IgA+ memory B cells in blood carry specific markers that may help to better understand IgA+ B cell biology.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":"e70191"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758213","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

Interferon-Regulatory Factor 4 Is Required Not Only for Induction but Also for Maintenance of the Th17 Phenotype. 干扰素调节因子4不仅是诱导和维持Th17表型所必需的。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-01 DOI: 10.1002/eji.70193

Janis Patten, Prema Erramsetti, Addi Josua Romero Olmedo, Olaf Pinkenburg, Magdalena Huber, Michael Lohoff

引用次数: 0

Accumulation of Siglec10⁺CX3CR1⁺ Macrophages in the Tumor Microenvironment of Glioblastomas. 胶质母细胞瘤微环境中Siglec10+CX3CR1+巨噬细胞的积累

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-01 DOI: 10.1002/eji.70180

Nico Andreas, Lucas Gath, Paul Mike Jordan, Saskia Steiner, Oliver Werz, Nazife Dinc, Peter Baumgarten, Christian Senft

{"title":"Accumulation of Siglec10+CX3CR1+ Macrophages in the Tumor Microenvironment of Glioblastomas.","authors":"Nico Andreas, Lucas Gath, Paul Mike Jordan, Saskia Steiner, Oliver Werz, Nazife Dinc, Peter Baumgarten, Christian Senft","doi":"10.1002/eji.70180","DOIUrl":"10.1002/eji.70180","url":null,"abstract":"Glioblastoma (GBM) is one of the most aggressive primary brain tumors in adults. Despite various strategies, including differential single-cell gene expression analyses between GBM and healthy tissues, none of the resulting findings could benefit the development of promising therapies, yet. Various macrophage populations coevolve in the tumor microenvironment of GBMs and not only support tumor immune evasion but also tumor spreading throughout the surrounding tissue. To distillate unique immune cell features of GBMs, we compared their immune cell composition with other central nervous system (CNS) tumor entities, in particular meningiomas (MNGs), non-GBM gliomas, and metastases (MTS). We could identify a macrophage population characterized by the coexpression of CX3CR1 and Siglec10, representing a potential indicator population of GBMs. This GBM-specific macrophage subset might be supported by a glioma-characteristic lipid mediator (LM) milieu of enriched docosahexaenoic acid (DHA) and its lipoxygenase (LOX)-derived metabolites. Moreover, the GBM tumor microenvironment (TME) is enriched in arachidonic acid (AA)-derived cyclooxygenase (COX) products prostaglandins (PG) E2 and F2α in combination with enhanced CD24 expression. By our comparative approach, the data hint toward a pro-tumorigenic Siglec10+CX3CR1+ macrophage population depending on the characteristic tumor microenvironment (TME) of highly malignant GBMs.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":"e70180"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721115","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

EXPRESSION OF CONCERN: Activation of Epstein-Barr Virus/C3d Receptor (gp140, CR2, CD21) on Human Cell Surface Triggers pp60src and Akt-GSK3 Activities Upstream and Downstream to PI 3-Kinase, Respectively. 关注的表达：Epstein-Barr病毒/C3d受体（gp140, CR2, CD21）在人细胞表面的激活分别触发pp60src和Akt-GSK3在PI 3激酶上游和下游的活性。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-01 DOI: 10.1002/eji.70187

引用次数: 0

ADAR1 Controls Macrophage Scavenging and Lipid-Buffering Programs in Metabolic Tissues. ADAR1控制代谢组织中巨噬细胞清除和脂质缓冲程序。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-01 DOI: 10.1002/eji.70189

Achilleas Fardellas, Emelie Barreby, Madara Brice, Sebastian Nock, Jules Russick, Ana Vankova, Charlotte Edberg, Ida Robertsen, Jens K Hertel, Per Stål, Gunnar Mellgren, Cecilia Karlsson, Jøran S Hjelmesaeth, Hannes Hagström, Erik Näslund, Volker M Lauschke, Johan Fernø, Ping Chen, Cecilia Morgantini, Myriam Aouadi, Niklas K Björkström

{"title":"ADAR1 Controls Macrophage Scavenging and Lipid-Buffering Programs in Metabolic Tissues.","authors":"Achilleas Fardellas, Emelie Barreby, Madara Brice, Sebastian Nock, Jules Russick, Ana Vankova, Charlotte Edberg, Ida Robertsen, Jens K Hertel, Per Stål, Gunnar Mellgren, Cecilia Karlsson, Jøran S Hjelmesaeth, Hannes Hagström, Erik Näslund, Volker M Lauschke, Johan Fernø, Ping Chen, Cecilia Morgantini, Myriam Aouadi, Niklas K Björkström","doi":"10.1002/eji.70189","DOIUrl":"https://doi.org/10.1002/eji.70189","url":null,"abstract":"Adenosine deaminase acting on RNA 1 (ADAR1) regulates mRNA fate and function through adenosine-to-inosine (A-to-I) RNA editing and RNA-binding activities. While its role in innate immunity is established, the broader regulatory functions of ADAR1 in macrophages remain poorly defined. Here, we systematically profiled ADAR1 expression across human immune cells and identified marked enrichment in macrophages, driven by selective usage of an alternative transcription start site during monocyte-to-macrophage differentiation. ADAR1 binds, edits, and modulates key macrophage targets involved in efferocytosis, endocytosis, lysosomal processing, lipid metabolism, and proliferation in an isoform-specific manner. We further demonstrate that ADAR1 levels and activity are dynamically regulated in adipose tissue and liver during the progression of metabolic disease. Linked to this, macrophage-specific ablation of ADAR1 co-cultured in organotypic 3D primary human liver spheroids and exposed to metabolic stress resulted in an exacerbated lipid accumulation phenotype. Finally, we identify a lipid-associated macrophage-specific upregulation of ADAR1 in adipose tissue following weight loss interventions, mechanistically driven by free fatty acids. These findings uncover a previously unrecognized role for ADAR1 in lipid-buffering, scavenging, and proliferative macrophage functions, extending its biological relevance beyond canonical interferon-mediated immunity and establishing ADAR1 as a key regulator of macrophage adaptation in metabolic disease.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":"e70189"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757660","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

Dynamic Thymic Stromal Lymphopoietin and Its Receptor Complex Expression on Skin Langerhans Cells in Response to MC903-induced Skin Inflammation mc903诱导皮肤炎症的动态胸腺基质淋巴生成素及其受体复合物在皮肤朗格汉斯细胞中的表达

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-03-30 DOI: 10.1002/eji.70178

Martín I. González-Rodríguez, Tanja Salomaa, Carolina Cabalin, Tuomas Komulainen, Lotta Hiihtola, Laura Kummola, Tero A. H. Järvinen, Ilkka S. Junttila

引用次数: 0