European Journal of Immunology最新文献_第10页

Modulation of the K/BxN arthritis mouse model and the effector functions of human fibroblast-like synoviocytes by liver X receptors 肝X受体对K/BxN关节炎小鼠模型和人类成纤维细胞样滑膜细胞效应功能的调节作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-15 DOI: 10.1002/eji.202451136

María Jesús Domínguez-Luis, Javier Castro-Hernández, Sergio Santos-Concepción, Ana Díaz-Martín, Mayte Arce-Franco, Natán Pérez-González, Mercedes Díaz, Antonio Castrillo, Eduardo Salido, José David Machado, Mónica Gumá, Maripat Corr, Federico Díaz-González

{"title":"Modulation of the K/BxN arthritis mouse model and the effector functions of human fibroblast-like synoviocytes by liver X receptors","authors":"María Jesús Domínguez-Luis, Javier Castro-Hernández, Sergio Santos-Concepción, Ana Díaz-Martín, Mayte Arce-Franco, Natán Pérez-González, Mercedes Díaz, Antonio Castrillo, Eduardo Salido, José David Machado, Mónica Gumá, Maripat Corr, Federico Díaz-González","doi":"10.1002/eji.202451136","DOIUrl":"10.1002/eji.202451136","url":null,"abstract":"The role of liver X receptors (LXR) in rheumatoid arthritis (RA) remains controversial. We studied the effect of LXR agonists on fibroblast-like synoviocytes (FLS) from RA patients and the K/BxN arthritis model in LXRα and β double-deficient (Nr1h2/3−/−) mice. Two synthetic LXR agonists, GW3965 and T0901317, were used to activate LXRs and investigate their effects on cell growth, proliferation and matrix metalloproteinases, and chemokine production in cultured FLS from RA patients. The murine model K/BxN serum transfer of inflammatory arthritis in Nr1h2/3−/− animals was used to investigate the role of LXRs on joint inflammation in vivo. LXR agonists inhibited the FLS proliferative capacity in response to TNF, the chemokine-induced migration, the collagenase activity in FLS supernatant and FLS CXCL12 production. In the K/BxN mouse model, Nr1h2/3−/− animals showed aggravated arthritis, histological inflammation, and joint destruction, as well as an increase in synovial metalloproteases and expression of proinflammatory mediators such as IL-1β and CCL2 in joints compared with wild type animals. Taken together, these data underscore the importance of LXRs in modulating the joint inflammatory response and highlight them as potential therapeutic targets in RA.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986993","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

Phosphoantigen recognition by Vγ9Vδ2 T cells Vγ9Vδ2 T 细胞对磷酸抗原的识别。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-15 DOI: 10.1002/eji.202451068

Thomas Herrmann, Mohindar Murugesh Karunakaran

{"title":"Phosphoantigen recognition by Vγ9Vδ2 T cells","authors":"Thomas Herrmann, Mohindar Murugesh Karunakaran","doi":"10.1002/eji.202451068","DOIUrl":"10.1002/eji.202451068","url":null,"abstract":"Vγ9Vδ2 T cells comprise 1–10% of human peripheral blood T cells. As multifunctional T cells with a strong antimicrobial and antitumor potential, they are of strong interest for immunotherapeutic development. Their hallmark is the eponymous Vγ9Vδ2 T-cell antigen receptor (TCR), which mediates activation by so-called “phosphoantigens” (PAg). PAg are small pyrophosphorylated intermediates of isoprenoid synthesis of microbial or host origin, with the latter elevated in some tumors and after administration of aminobisphosphonates. This review summarizes the progress in understanding PAg-recognition, with emphasis on the interaction between butyrophilins (BTN) and PAg and insights gained by phylogenetic studies on BTNs and Vγ9Vδ2 T cells, especially the comparison of human and alpaca. It proposes a composite ligand model in which BTN3A1-A2/A3-heteromers and BTN2A1 homodimers form a Vγ9Vδ2 TCR activating complex. An initiating step is the binding of PAg to the intracellular BTN3A1-B30.2 domain and formation of a complex with the B30.2 domains of BTN2A1. On the extracellular surface this results in BTN2A1-IgV binding to Vγ9-TCR framework determinants and BTN3A-IgV to additional complementarity determining regions of both TCR chains. Unresolved questions of this model are discussed, as well as questions on the structural basis and the physiological consequences of PAg-recognition.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986994","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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Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption 原发性 HIV 感染期间的抗逆转录病毒疗法对治疗中断后 T 细胞免疫的影响。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-13 DOI: 10.1002/eji.202451200

Timothy Tipoe, Ane Ogbe, Ming Lee, Helen Brown, Nicola Robinson, Rebecca Hall, Claire Petersen, Heather Lewis, John Thornhill, Fiona Ryan, Julie Fox, Sarah Fidler, John Frater

{"title":"Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption","authors":"Timothy Tipoe, Ane Ogbe, Ming Lee, Helen Brown, Nicola Robinson, Rebecca Hall, Claire Petersen, Heather Lewis, John Thornhill, Fiona Ryan, Julie Fox, Sarah Fidler, John Frater","doi":"10.1002/eji.202451200","DOIUrl":"10.1002/eji.202451200","url":null,"abstract":"This study aims to understand the impact of early antiretroviral therapy (ART) on HIV-specific T-cell responses measured after treatment interruption, which may inform strategies to deliver ART-free immune-mediated viral suppression. HIV-specific T-cell immunity was analysed using gamma interferon enzyme-linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag-directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag-directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol-specific responses post-TI compared with pre-TI. Although early ART in PHI was not associated with major differences in HIV-specific immunity following TI compared with untreated participants, the potential to make more new Gag-directed responses warrants further investigation as this may inform strategies to achieve ART-free control.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974635","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

Nurturing the phenotype: Environmental signals and transcriptional regulation of intestinal γδ T cells 培养表型：肠道γδT细胞的环境信号和转录调控

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-13 DOI: 10.1002/eji.202451076

Lisa Vogg*, Thomas H. Winkler

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Impressum 印象深刻

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-07 DOI: 10.1002/eji.202470083

引用次数: 0

Issue Information: Eur. J. Immunol. 8'24 发行信息：Eur.J. Immunol.

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-07 DOI: 10.1002/eji.202470082

引用次数: 0

Cover Story: Eur. J. Immunol. 8'24 封面故事Eur.J. Immunol.8'24

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-07 DOI: 10.1002/eji.202470081

引用次数: 0

Characteristics and mechanisms of T-cell senescence: A potential target for cancer immunotherapy T 细胞衰老的特征和机制：癌症免疫疗法的潜在靶点

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-06 DOI: 10.1002/eji.202451093

Han Wu, Junru Li, Zhen Zhang, Yi Zhang

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Correct stimulation of CD28H arms NK cells against tumor cells 正确刺激 CD28H 武器 NK 细胞对抗肿瘤细胞。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-05 DOI: 10.1002/eji.202350901

Raphaëlle Leau, Pierre Duplouye, Virginie Huchet, Véronique Nerrière-Daguin, Bernard Martinet, Mélanie Néel, Martin Morin, Richard Danger, Cécile Braudeau, Régis Josien, Gilles Blancho, Fabienne Haspot

{"title":"Correct stimulation of CD28H arms NK cells against tumor cells","authors":"Raphaëlle Leau, Pierre Duplouye, Virginie Huchet, Véronique Nerrière-Daguin, Bernard Martinet, Mélanie Néel, Martin Morin, Richard Danger, Cécile Braudeau, Régis Josien, Gilles Blancho, Fabienne Haspot","doi":"10.1002/eji.202350901","DOIUrl":"10.1002/eji.202350901","url":null,"abstract":"Tumor evasion has recently been associated with a novel member of the B7 family, HERV-H LTR-associating 2 (HHLA2), which is mostly overexpressed in PDL-1neg tumors. HHLA2 can either induce a costimulation signal when bound to CD28H or inhibit it by binding to KIR3DL3 on T- and NK cells. Given the broad distribution of CD28H expression on NK cells and its role, we compared two monoclonal antibodies targeting this novel NK-cell engager in this study. We show that targeting CD28H at a specific epitope not only strongly activates Ca2+ flux but also results in NK-cell activation. CD28H-activated NK cells further display increased cytotoxic activity against hematopoietic cell lines and bypass HHLA2 and HLA-E inhibitory signals. Additionally, scRNA-seq analysis of clear cell renal cancer cells revealed that HHLA2+ clear cell renal cancer cell tumors were infiltrated with CD28H+ NK cells, which could be targeted by finely chosen anti-CD28H Abs.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202350901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887763","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 complement model disease paroxysmal nocturnal hemoglobinuria 补体模型病阵发性夜间血红蛋白尿。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-05 DOI: 10.1002/eji.202350817

Christoph Q. Schmidt, Britta Höchsmann, Hubert Schrezenmeier

{"title":"The complement model disease paroxysmal nocturnal hemoglobinuria","authors":"Christoph Q. Schmidt, Britta Höchsmann, Hubert Schrezenmeier","doi":"10.1002/eji.202350817","DOIUrl":"10.1002/eji.202350817","url":null,"abstract":"We describe initial, current, and future aspects of complement activation and inhibition in the rare hematological disease paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare but severe hematological disorder characterized by complement-mediated intravascular hemolysis resulting in anemia and severe thrombosis. Insights into the complement-mediated pathophysiology ultimately led to regulatory approval of the first-in-class complement inhibitor, eculizumab, in 2007. This anti-complement C5 therapy resulted in the stabilization of many hematologic parameters and dramatically reduced the often fatal, coagulant-resistant thrombotic events. Despite the remarkable clinical success, a substantial proportion of PNH patients experience suboptimal clinical responses during anti-C5 therapy. We describe the identification and mechanistic dissection of four unexpected processes responsible for such suboptimal clinical responses: (1) pharmacokinetic and (2) pharmacodynamic intravascular breakthrough hemolysis, (3) continuing low-level residual intravascular hemolysis, and (4) extravascular hemolysis. Novel complement therapeutics mainly targeting different complement proteins proximal in the cascade attempt to address these remaining problems. With five approved complement inhibitors in the clinic and many more being evaluated in clinical trials, PNH remains one of the complement diseases with the highest intensity of clinical research. Mechanistically unexpected breakthrough events occur not only with C5 inhibitors but also with proximal pathway inhibitors, which require further mechanistic elaboration.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202350817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887764","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