Journal of immunology最新文献_第7页

Immune mechanisms and signatures in lethal and non-lethal sepsis revealed by single-cell transcriptomics. 单细胞转录组学揭示致死性和非致死性败血症的免疫机制和特征。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf140

Xinyang Zhang, Yunshi Cao, Zihui Zhao, Lijie Tang, Baozhong Zhang, Chunyu Liao, Ganwu Li, Wentong Cai

{"title":"Immune mechanisms and signatures in lethal and non-lethal sepsis revealed by single-cell transcriptomics.","authors":"Xinyang Zhang, Yunshi Cao, Zihui Zhao, Lijie Tang, Baozhong Zhang, Chunyu Liao, Ganwu Li, Wentong Cai","doi":"10.1093/jimmun/vkaf140","DOIUrl":"10.1093/jimmun/vkaf140","url":null,"abstract":"Sepsis is a life-threatening inflammatory syndrome caused by systemic infections, potentially leading to multi-organ failure and death. Due to patient heterogeneity, early and accurate diagnosis of sepsis, as well as stratification of patients by severity and potential outcomes, remains a huge challenge. In this study, we leveraged the genetic homogeneity of inbred mice to develop Escherichia coli-induced lethal and non-lethal sepsis models. Using single-cell RNA sequencing, we analyzed dynamic transcriptomes of peripheral blood mononuclear cells and found a marked expansion of monocytes during sepsis. A specific monocyte subset, designated Mono2, exhibited heightened expression of cytokines, chemokines, and pro-inflammatory pathways compared to other subsets. Notably, we observed a clear increasing trend in the abundance of Mono2 population in the lethal groups, and a decreasing trend in the non-lethal groups over time. Genes enriched in pro-inflammatory pathways (eg TNF and NF-κB signaling pathways) showed opposing trends in the 2 models: decreasing as mice recovered in the non-lethal model and increasing as mice succumbed to infection in the lethal model. Furthermore, we identified gene signatures corresponding to different stages of infection in the mouse models. By utilizing publicly available patient data, we validated the diagnostic potential of several genes and gene sets, including ANXA1+FPR1 and BCL2A1 for distinguishing septic patients from healthy individuals, and GBP2 for differentiating survivors from non-survivors. Collectively, this study highlights critical cellular and molecular signatures while providing insights into host immune mechanisms underlying sepsis progression and outcomes, offering valuable resources for advancing sepsis diagnosis and therapeutic strategies.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2338-2356"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528281","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

RGS1 is an effective T-cell marker of acute myeloid leukemia remission after hematopoietic stem cell transplantation. RGS1是造血干细胞移植后急性髓系白血病缓解的有效t细胞标志物。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf096

Yue Ren, Li-Ting Niu, Xin-Yu Dong, Yu-Qing Wang, Xiao-Jun Huang, Xiang-Yu Zhao

{"title":"RGS1 is an effective T-cell marker of acute myeloid leukemia remission after hematopoietic stem cell transplantation.","authors":"Yue Ren, Li-Ting Niu, Xin-Yu Dong, Yu-Qing Wang, Xiao-Jun Huang, Xiang-Yu Zhao","doi":"10.1093/jimmun/vkaf096","DOIUrl":"10.1093/jimmun/vkaf096","url":null,"abstract":"Disease relapse is a major cause of death in acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The characterization of novel functional T-cell subtypes is critical for predicting clinical responses as well as developing strategies for immunotherapy in leukemia. We used single-cell RNA-sequencing to resolve the T cells' profiles of AML patients who had a relapse (RL) or reached complete remission (CR) after HSCT and addressed the characteristics of T cells at molecular level under HSCT scenario. Ten T-cell subtypes were identified in these RL and CR patient groups, of which mature T cells subtypes, such as CD8+ T effector memory (TEM), CD8+ T effector (TEFF), CD4+ TEM, and CD4+ TEFF cells, tended to be more abundant in the CR group, while naïve CD8, naïve CD4, and exhausted CD8+ T cells occupied larger proportions in the RL group. Of note, we identified that RGS1 (regulator of G-protein signaling 1) highly expressing CD8+ TEFFs tended to enrich in the CR group. Higher levels of RGS1 in CD8+ TEFF, CD8+ T, and CD3+ T cells were significantly associated with remission after HSCT in AML patients, which could also predict clinical outcomes after allo-HSCT. And the elevation of RGS1 levels in CD8+ T cells increased cytotoxic factor production, possibly by activating the NF-κB signaling pathway. These findings provide valuable insights into T-cell characteristics under allo-HSCT and identify RGS1 as a new marker potentially predicting clinical responses for AML after allo-HSCT.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2434-2452"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266427","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

NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression. NC410是一种二价lir -2构建物，在肿瘤微环境中重塑胶原，并消除中性粒细胞驱动的T细胞抑制。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf121

Thejaswini Giridharan, Sora Suzuki, Anm Nazmul H Khan, Qian Liu, Kristopher Attwood, Anna Stokolosa, Sidney Mahan, Agnieszka K Witkiewicz, Janine Joseph, Kirsten Moysich, Solomon Langermann, Rustin Lovewell, Dallas Flies, Han Myint, Kunle Odunsi, Tiffany R Emmons, Michael B Yaffe, Emese Zsiros, Prasenjit Dey, A J Robert McGray, Brahm H Segal

{"title":"NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression.","authors":"Thejaswini Giridharan, Sora Suzuki, Anm Nazmul H Khan, Qian Liu, Kristopher Attwood, Anna Stokolosa, Sidney Mahan, Agnieszka K Witkiewicz, Janine Joseph, Kirsten Moysich, Solomon Langermann, Rustin Lovewell, Dallas Flies, Han Myint, Kunle Odunsi, Tiffany R Emmons, Michael B Yaffe, Emese Zsiros, Prasenjit Dey, A J Robert McGray, Brahm H Segal","doi":"10.1093/jimmun/vkaf121","DOIUrl":"10.1093/jimmun/vkaf121","url":null,"abstract":"We previously observed that circulating human neutrophils exposed to epithelial ovarian cancer (OC) ascites fluid supernatants (ASC) and malignant effusions from other tumors acquire T cell suppressor function. Collagen motifs ligate LAIR-1, an inhibitory SHP-1-dependent checkpoint broadly expressed on immune cells. We hypothesized that NC410, a bivalent LAIR-2 construct that inhibits LAIR-1-collagen binding, would rescue neutrophil-driven T cell non-responsiveness. NC410 remodeled ASC collagen resulting in neutrophil clustering and reduction in neutrophil-T cell contact, abrogated ASC-induced neutrophil trogocytosis of T cell membranes and rescued stimulated T cell proliferation. Mean ASC pro-collagen-1α levels were >100-fold greater than serum samples. In a single-center retrospective analysis, after adjusting for age, stage and optimal debulking, ASC pro-collagen-1α and serum sLAIR-1 levels were each associated with worse overall survival (OS), and ASC LAIR-2 levels were associated with better OS. Multispectral imaging of high-grade serous ovarian cancer and non-small cell lung cancer showed highly variable LAIR-1 staining in both tumor cell and immune infiltrates. The proportion of collagen-1-positive cells was highest among tumor cells and tumor-infiltrating immune cells versus stromal immune cells, raising the potential role of tumor-associated collagen limiting immune cell infiltration into tumor. Our results support further evaluation of circulating and tumor-associated collagen products and LAIR-1 and LAIR-2 as prognostic biomarkers in advanced OC and as biomarkers for clinical response to NC410 and to other collagen- and LAIR-directed therapies.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2464-2479"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484734","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

RasGRP1 signaling is required for Vγ2+ thymocyte c-Maf expression and γδT17 lineage programming. RasGRP1信号是v - γ - 2+胸腺细胞c-Maf表达和γ - δ t17谱系编程所必需的。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf230

Kevin Joannou, Dominic P Golec, Abul K Azad, Laura M Henao Caviedes, Julia F May, Ress G Kelly, Troy A Baldwin

{"title":"RasGRP1 signaling is required for Vγ2+ thymocyte c-Maf expression and γδT17 lineage programming.","authors":"Kevin Joannou, Dominic P Golec, Abul K Azad, Laura M Henao Caviedes, Julia F May, Ress G Kelly, Troy A Baldwin","doi":"10.1093/jimmun/vkaf230","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf230","url":null,"abstract":"The γδ TCR instructively directs both lineage specification and effector programming of developing γδ T cells. However, the way in which different TCR signal strengths and other auxiliary signals coordinate downstream of the γδ TCR to regulate γδ T-cell development remains unclear. In this study we defined the role of Ras guanyl-releasing protein 1 (RasGRP1) in the development and effector programming of γδ T cells. While RasGRP1 was not necessary for bulk γδ T-cell generation, we found it was required for efficient generation of Vγ4+ thymocytes and lineage-committed CD73+ γδ T cells in the thymus and periphery. Despite a decrease in immature CD73+ γδ thymocytes, there was an expansion of the perinatally derived CD8+IFNγ+ γδ T-cell population in the absence of RasGRP1. IL-17-producing γδ T cells were significantly reduced in RasGRP1 knockout mice, with a specific loss of Vγ2+ γδ T cells that corresponded to a loss of c-Maf expression as early as the DN1d thymocyte stage. Critically, these cells undergoing γδT17 programming in adults could express c-Maf in response to CCR9 stimulation, with RasGRP1 but not MEK activity being required for CCR9-induced c-Maf expression. Thus, RasGRP1 activation serves as an important signaling hub in the effector programming of γδ T cells, which integrates signals from both non-TCR and TCR inputs to direct differentiation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957078","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

Modulatory effects of M3 muscarinic acetylcholine receptor on inflammatory profiles of human memory T helper cells. M3毒蕈碱乙酰胆碱受体对人记忆T辅助细胞炎症谱的调节作用。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf086

Fatemeh Gholizadeh, Mehri Hajiaghayi, Jennifer S Choi, Samuel R Little, Niloufar Rahbari, Melika Kargar, Kelly Brotto, Eric Han, Steve C C Shih, Peter J Darlington

{"title":"Modulatory effects of M3 muscarinic acetylcholine receptor on inflammatory profiles of human memory T helper cells.","authors":"Fatemeh Gholizadeh, Mehri Hajiaghayi, Jennifer S Choi, Samuel R Little, Niloufar Rahbari, Melika Kargar, Kelly Brotto, Eric Han, Steve C C Shih, Peter J Darlington","doi":"10.1093/jimmun/vkaf086","DOIUrl":"10.1093/jimmun/vkaf086","url":null,"abstract":"Memory T helper (Th) cells, generated in response to immunogenic challenges, are crucial in orchestrating adaptive immune responses. Acetylcholine (ACh), a key neurotransmitter of the parasympathetic nervous system, modulates immune function via muscarinic ACh receptors (mAChRs). This study investigates the role of mAChRs, particularly the M3 muscarinic ACh receptor (M3R), in regulating the cytokine and chemokine profile and NF-κB p65 activity in primary human memory Th cells. Memory Th cells were isolated from healthy donors and stimulated with anti-CD3/CD28/CD2 in the presence of oxotremorine-M (M1R-M5R agonist), atropine (M1R-M5R antagonist), or J104129 (M3R-selective antagonist). CHRM1-CHRM5 expression was quantified using RT-qPCR. M3R and phosphorylated NF-κB p65 were analyzed by Western blot. IFN-γ, IL-17A, and IL-4 were assessed by ELISA, while intracellular cytokine and chemokine receptor expression were measured by flow cytometry. CHRM3 knockout was performed using CRISPR-Cas9. Memory Th cells expressed all 5 mAChR subtypes. Oxotremorine-M increased IFN-γ and IL-17A while reducing IL-4 in an atropine-sensitive manner. Blocking or knocking out M3R prevented oxotremorine-M-induced increases in IFN-γ and IL-17A, but the suppression of IL-4 remained unchanged. Stimulation of mAChRs, particularly M3R, enhanced NF-κB p65 activity but did not affect chemokine receptor expression, cell proliferation, viability, or M3R levels. These findings indicate that mAChRs, including M3R, drive a pro-inflammatory memory Th-cell response through NF-κB p65 activation, while IL-4 suppression occurs independently of M3R. Targeting M3R specifically may provide a strategy for modulating adaptive immunity and treating inflammatory diseases.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2244-2255"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127855","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

The role of VISTA engagement in limiting neutrophil-mediated inflammation. VISTA参与限制中性粒细胞介导的炎症的作用。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf132

Elizabeth C Nowak, Jiannan Li, Zachary T Peters, Lindsay K Mendyka, Mohamed A ElTanbouly, Wilson L Davis, Petra Sergent, J Louise Lines, Nicole C Smits, Rodwell Mabaera, Shibani Rajanna, Catherine Carriere, Brent Koehn, Jeremy Allred, Bruce R Blazar, Christopher M Burns, Randolph J Noelle, Sladjana Skopelja-Gardner

{"title":"The role of VISTA engagement in limiting neutrophil-mediated inflammation.","authors":"Elizabeth C Nowak, Jiannan Li, Zachary T Peters, Lindsay K Mendyka, Mohamed A ElTanbouly, Wilson L Davis, Petra Sergent, J Louise Lines, Nicole C Smits, Rodwell Mabaera, Shibani Rajanna, Catherine Carriere, Brent Koehn, Jeremy Allred, Bruce R Blazar, Christopher M Burns, Randolph J Noelle, Sladjana Skopelja-Gardner","doi":"10.1093/jimmun/vkaf132","DOIUrl":"10.1093/jimmun/vkaf132","url":null,"abstract":"A growing body of evidence suggests that the immune checkpoint inhibitory receptor VISTA plays a central role in the regulation of innate immunity in the settings of inflammatory diseases and cancer. Neutrophils are among the cells that have the highest membrane density of surface VISTA. In this study, targeting VISTA on neutrophils with a monoclonal antibody resulted in a striking reduction in their lipopolysaccharide (LPS)- and chemokine-induced peripheral accumulation but did not reduce neutrophil levels at steady state. Fc receptor engagement and macrophages were required for the effects of anti-VISTA antibody on neutrophils. Concomitant with reduced peripheral neutrophil numbers, targeting VISTA increased neutrophil clearance by macrophages in the liver. In a murine model of neutrophil-mediated arthritis, anti-VISTA antibody treatment ameliorated disease severity, which was associated with reduced myeloperoxidase activity in the joints. These studies identify a novel therapeutic opportunity for targeting VISTA to control neutrophil-mediated inflammation and tissue injury.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2385-2396"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505955","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

HMGB1 inhibits the IFN-γ-induced PD-L1 expression in NSCLC. HMGB1抑制IFN-γ诱导的PD-L1在非小细胞肺癌中的表达。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf125

Shumin Wang, Feng Li, Liubo Zhang, Yu Ping, Wenhao Hu, Qun Gao, Qitai Zhao, Kai Zhang, Yibo Huang, Bin Zhang, Yi Zhang

{"title":"HMGB1 inhibits the IFN-γ-induced PD-L1 expression in NSCLC.","authors":"Shumin Wang, Feng Li, Liubo Zhang, Yu Ping, Wenhao Hu, Qun Gao, Qitai Zhao, Kai Zhang, Yibo Huang, Bin Zhang, Yi Zhang","doi":"10.1093/jimmun/vkaf125","DOIUrl":"10.1093/jimmun/vkaf125","url":null,"abstract":"T cells are the most important cytotoxic cells involved in antitumor immune responses. After recognizing the major histocompatibility complex (MHC)-peptide complex, cytokines including interferon-γ (IFN-γ) are released to kill tumor cells. However, IFN-γ can also induce tumor cells to express PD-L1. This molecule can bind to PD-1 on the surface of T cells to exert inhibitory functions. In response to stimuli, like chemoradiotherapy or immunotherapy, tumor cells release damage-associated molecular patterns, including high-mobility group protein B1 (HMGB1). Our previous studies revealed that HMGB1 can increase the antitumor activity of T cells and enhance the secretion of cytokines, including IFN-γ. However, the effect of HMGB1 on PD-L1 expression in non-small cell lung cancer remains unclear. Here, we examined the expression of HMGB1 and PD-L1 in tumor tissue slices of patients with non-small cell lung cancer with high expression of IFN-γ and observed that they exhibited a negative correlation, which was also verified by our analysis in The Cancer Genome Atlas. In vitro experiments demonstrated that HMGB1 could bind to RAGE (receptor for advanced glycation end products) and inhibit IFN-γ induction of PD-L1 by inhibiting the JAK1/STAT3 pathway. In vitro and in vivo experiments indicated that HMGB1 enhanced the antitumor effects of chimeric antigen receptor T cells and inhibited tumor growth. These results showed that HMGB1 inhibited IFN-γ-induced PD-L1 expression, thereby enhancing the antitumor effects of T cells, and confirmed the role of HMGB1 as a prognostic indicator for lung cancer treated with chimeric antigen receptor T cells.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2480-2488"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528280","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

The 4 functional segments of Factor H: Role in physiological target recognition and contribution to disease. 因子H的4个功能片段：在生理靶标识别中的作用和对疾病的贡献。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf065

Peter F Zipfel, Karin Heidenreich

{"title":"The 4 functional segments of Factor H: Role in physiological target recognition and contribution to disease.","authors":"Peter F Zipfel, Karin Heidenreich","doi":"10.1093/jimmun/vkaf065","DOIUrl":"10.1093/jimmun/vkaf065","url":null,"abstract":"Factor H controls proximal complement activation, and its dysfunction leads to diseases that often manifest in the kidney. Structural and functional analyses have identified 4 distinct functional segments: an N-terminal regulatory unit, a cell binding unit, a segment with combined low-affinity C3b and heparin sites, and a C-terminal recognition or sensor unit with overlapping C3b/C3d and heparin sites. Three segments are linked to diseases. The regulatory segment is affected in C3 glomerulopathy and antineutrophil cytoplasmic antibody-associated vasculitis. The second segment includes the Y402H polymorphism of age-related macular degeneration, is associated with different types of cancer, and is targeted by pathogens. The C-terminal sensor segment is involved in atypical hemolytic uremic syndrome, in FHR1:FHR3 deficient and autoantibody-positive hemolytic uremic syndrome form and is exploited by pathogens. Factor H function is modulated by Factor H like protein 1 and FHR1, 2 plasma proteins that share segments with Factor H. This interplay is critical for fine-tuning local complement. Understanding Factor H's physiological role, as well as the impact of its absence, mutations, or autoantibody targeting, provides insights into disease mechanisms and provides opportunities for therapeutic intervention by using full-length Factor H, its fragments, or complement-modulatory compounds.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2150-2164"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970153","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

Specific thresholds of circulating antibody titers predict against infection and reduced disease severity in SARS-CoV-2 close contacts. 循环抗体滴度的特定阈值预测SARS-CoV-2密切接触者的感染和疾病严重程度降低。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf101

Joanne Byrne, Colette Marie Gaillard, Lili Gu, Alejandro Garcia-Leon, Orlaith Casey, Grace Kenny, Gurvin Saini, Dana Alalwan, Tessa O'Gorman, Siobhan O'Regan, Peter Doran, Eoin R Feeney, Jane A O'Halloran, Mary Horgan, Aoife G Cotter, Eoghan de Barra, Corinna Sadlier, Alan Landay, Virginie Gautier, Patrick W G Mallon

{"title":"Specific thresholds of circulating antibody titers predict against infection and reduced disease severity in SARS-CoV-2 close contacts.","authors":"Joanne Byrne, Colette Marie Gaillard, Lili Gu, Alejandro Garcia-Leon, Orlaith Casey, Grace Kenny, Gurvin Saini, Dana Alalwan, Tessa O'Gorman, Siobhan O'Regan, Peter Doran, Eoin R Feeney, Jane A O'Halloran, Mary Horgan, Aoife G Cotter, Eoghan de Barra, Corinna Sadlier, Alan Landay, Virginie Gautier, Patrick W G Mallon","doi":"10.1093/jimmun/vkaf101","DOIUrl":"10.1093/jimmun/vkaf101","url":null,"abstract":"Higher circulating SARS-CoV-2 IgG titers correlate with SARS-CoV-2 ex vivo viral neutralization, but how well this translates to clinical protection in the real-world setting is unclear. In a prospective cohort study, we enrolled 44 SARS-CoV-2 negative, confirmed SARS-CoV-2 close contacts. Receptor-binding domain (RBD) and full-spike IgG and SARS-CoV-2 memory B-cell frequencies were measured at exposure, and participants were serially tested for incident infection over 14 days. Those who developed SARS-CoV-2 infection had significantly lower RBD titers, but not memory B-cell frequencies. An RBD IgG titer >6321 BAU/ml was associated with a reduced SARS-CoV-2 acquisition risk (HR 0.32, 95% CI 0.13-0.81), while an RBD IgG titer >456 BAU/ml was associated with a reduced moderate or severe COVID-19 risk (HR 0.15, 95% CI 0.03-0.81), identifying this threshold as a correlate of protection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2238-2243"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127857","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

The complement regulator CD55 modulates TLR9 signaling and supports survival in marginal zone B cells. 补体调节剂CD55调节TLR9信号并支持边缘区B细胞的存活。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf124

Iris Lee, Xi Wang, Ivana Ling, Sonam Verma, Cassaundra Eck, Wumei Blanche, Christine T N Pham, Peggy L Kendall

{"title":"The complement regulator CD55 modulates TLR9 signaling and supports survival in marginal zone B cells.","authors":"Iris Lee, Xi Wang, Ivana Ling, Sonam Verma, Cassaundra Eck, Wumei Blanche, Christine T N Pham, Peggy L Kendall","doi":"10.1093/jimmun/vkaf124","DOIUrl":"10.1093/jimmun/vkaf124","url":null,"abstract":"Marginal zone (MZ) B cells bridge innate and adaptive immunity by sensing bloodborne antigens and producing rapid antibody and cytokine responses. When unregulated, MZ B cells are associated with autoimmunity. CD55 is a membrane-bound complement regulator that interferes with complement activation and is another important component of innate and adaptive immunity. MZ B cells express low CD55 in both mice and humans, but the role of CD55 in MZ B cell function is unknown. Using germline knockout (KO) mice, we found that similar numbers of MZ B cells were initially established in 3-wk-old CD55-deficient mice compared with wild-type mice. However, MZ B cells failed to accumulate as mice aged and underwent increased apoptosis independent of alternative complement activation. Following ex vivo stimulation of MZ B cells through TLR9 (Toll-like receptor 9), we observed increased interleukin-6 expression in CD55 KO MZ B cells. In addition, CD55 KO mice exhibited reduced total IgG response following in vivo administration of TLR9 agonist. These findings provide new insights into the role of CD55 in MZ B cell survival and B cell function.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2211-2220"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505954","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