European Journal of Immunology最新文献_第7页

The complement system: A key player in the host response to infections 补体系统：宿主应对感染的关键角色。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-27 DOI: 10.1002/eji.202350814

Archana Jayaraman, Sarah Walachowski, Markus Bosmann

{"title":"The complement system: A key player in the host response to infections","authors":"Archana Jayaraman, Sarah Walachowski, Markus Bosmann","doi":"10.1002/eji.202350814","DOIUrl":"10.1002/eji.202350814","url":null,"abstract":"Infections are one of the most significant healthcare and economic burdens across the world as underscored by the recent coronavirus pandemic. Moreover, with the increasing incidence of antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions to design effective treatment strategies. The complement system is a key arsenal of the host defense response to pathogens and bridges both innate and adaptive immunity. However, in the contest between pathogens and host defense mechanisms, the host is not always victorious. Pathogens have evolved several approaches, including co-opting the host complement regulators to evade complement-mediated killing. Furthermore, deficiencies in the complement proteins, both genetic and therapeutic, can lead to an inefficient complement-mediated pathogen eradication, rendering the host more susceptible to certain infections. On the other hand, overwhelming infection can provoke fulminant complement activation with uncontrolled inflammation and potentially fatal tissue and organ damage. This review presents an overview of critical aspects of the complement-pathogen interactions during infection and discusses perspectives on designing therapies to mitigate complement dysfunction and limit tissue injury.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202350814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071559","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

19th European Meeting on Complement in Human Diseases, September 2–6, 2024, Lübeck, Germany 特刊：第 19 届欧洲人类疾病补体会议，2024 年 9 月 2-6 日，德国吕贝克。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-22 DOI: 10.1002/eji.202470300

引用次数: 0

Atg16l2 augments Nlrc4 inflammasome activation by facilitating NAIPs–NLRC4 association Atg16l2通过促进NAIPs-NLRC4的结合来增强Nlrc4炎性体的激活。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-22 DOI: 10.1002/eji.202451078

Zhoujin Wen, Tianli Yuan, Jiamin Liu, Dongyang Wang, Jun Ni, Xuehan Yan, Jian Tang, Jiayin Tang, Xuefeng Wu, Zheng Wang

{"title":"Atg16l2 augments Nlrc4 inflammasome activation by facilitating NAIPs–NLRC4 association","authors":"Zhoujin Wen, Tianli Yuan, Jiamin Liu, Dongyang Wang, Jun Ni, Xuehan Yan, Jian Tang, Jiayin Tang, Xuefeng Wu, Zheng Wang","doi":"10.1002/eji.202451078","DOIUrl":"10.1002/eji.202451078","url":null,"abstract":"As cytoplasmic protein complexes that are pivotal for innate immunity, inflammasomes act primarily through the detection of pathogen- or danger-associated molecular patterns. Nucleotide oligomerisation domain-like receptor family and caspase activation recruitment domain-containing protein 4 (NLRC4) inflammasomes identify and eliminate intracellular pathogens, a process contingent on the ligand-recognition capabilities of neuronal apoptosis inhibitory proteins (NAIPs). Upon detection of specific molecules indicative of intracellular infection, NAIPs discern distinct pathogenic components and subsequently transmit signals to NLRC4, thus initiating their activation and triggering an inflammatory response. However, the mechanisms underlying NLRC4 inflammasome remain unclear. In this study, we elucidated the critical role of ATG16L2 in activating the NLRC4 inflammasome. ATG16L2-deficient macrophages exhibited reduced NLRC4 inflammasome activation, characterised by decreased oligomerisation of apoptosis-associated speck-like protein containing a CARD and attenuated cleavage of Pro-caspase-1, Pro-IL-1β and gasdermin D. Co-immunoprecipitation assays revealed an interaction between ATG16L2 and NAIPs. Furthermore, ATG16L2 enhanced the association between NAIPs and NLRC4 by binding to NAIPs. For ATG16L2-knockout mice infected with Salmonella typhimurium, pathogen clearance and survival rates markedly decreased. Collectively, our findings suggest that ATG16L2 is a significant modulator of the innate immune system, influencing the activity of the NLRC4 inflammasome and the host's defensive response to intracellular pathogens.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034661","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

7th European Conference of Immunology, 1–4 September, 2024, Dublin, Ireland 第 7 届欧洲免疫学会议，2024 年 9 月 1-4 日，爱尔兰都柏林

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-21 DOI: 10.1002/eji.202470200

引用次数: 0

Circulating levels of endogenous complement inhibitors correlate inversely with complement consumption in systemic lupus erythematosus 循环中的内源性补体抑制剂水平与系统性红斑狼疮患者的补体消耗量成反比。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-08-20 DOI: 10.1002/eji.202450998

Stef van der Meulen, Rory C. Monahan, Kyra A. Gelderman, Cees van Kooten, Y.K. Onno Teng, Tom W.J. Huizinga, Gerda M. Steup-Beekman, Leendert A. Trouw

{"title":"Circulating levels of endogenous complement inhibitors correlate inversely with complement consumption in systemic lupus erythematosus","authors":"Stef van der Meulen, Rory C. Monahan, Kyra A. Gelderman, Cees van Kooten, Y.K. Onno Teng, Tom W.J. Huizinga, Gerda M. Steup-Beekman, Leendert A. Trouw","doi":"10.1002/eji.202450998","DOIUrl":"10.1002/eji.202450998","url":null,"abstract":"Systemic lupus erythematosus (SLE) is marked by excessive complement activation, contributing to tissue damage. Complement activation can be detected in many organs including the skin, kidney, and brain. The involvement of the central nervous system is particularly relevant to understanding neuropsychiatric SLE (NPSLE), one of the poorest understood manifestations of SLE for which no biomarkers are available. We studied the levels of complement inhibitors in SLE in relation to disease activity and as possible biomarkers to identify NPSLE. Serum levels of complement inhibitors C1-inhibitor (C1-INH), C4b-binding protein (C4BP), Factor I, and Factor H were measured in 345 SLE patients (including 102 with NPSLE) and 108 healthy controls. Compared with controls, SLE patients had higher C1-INH and C4BP but lower Factor I and H levels. All inhibitors positively correlated with total C3 and C4 levels. While correlating with the SLE Disease Activity Index (SLEDAI), no distinction in inhibitor levels was found between SLE and NPSLE patients. Over time, C1-INH and Factor H levels normalized, but no significant changes were observed for C4BP and Factor I. In SLE the levels of circulating complement inhibitors are inversely correlated to complement consumption but do not serve as biomarkers for NPSLE.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202450998","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007948","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

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}

引用次数: 0

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

引用次数: 0

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