BMC ImmunologyPub Date : 2025-02-28DOI: 10.1186/s12865-025-00691-x
Yingzhao Liu, Zhangwei Zhu, Qian Xu, Juan Xu, Jie Xing, Shengjun Wang, Huiyong Peng
{"title":"Identification of BTK as an immune-related biomarker for Hashimoto's thyroiditis by integrated bioinformatic analysis.","authors":"Yingzhao Liu, Zhangwei Zhu, Qian Xu, Juan Xu, Jie Xing, Shengjun Wang, Huiyong Peng","doi":"10.1186/s12865-025-00691-x","DOIUrl":"10.1186/s12865-025-00691-x","url":null,"abstract":"<p><strong>Background: </strong>Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders characterized by diffuse enlargement of the thyroid gland, lymphocyte infiltration, and thyroid-specific autoantibodies. Cellular and humoral immune disorders have been implicated in the development of HT. However, little is known regarding the role of immune-related molecules in HT. This study was aimed to identify key immune-related biomarkers in HT by using bioinformatic analysis.</p><p><strong>Method: </strong>Integration of the sequencing data from HT and normal control (NC) in the GSA and GTEx databases yielded a dataset named NGS. The GSE138198 dataset from the GEO database was downloaded as a validation set. WGCNA analysis was performed to identify key modules associated with HT. Lasso regression analysis (LASSO) and random forest (RF) were performed to determine potential diagnostic biomarkers. The potential value was assessed by using receiver operating characteristic (ROC) curve analysis. CIBERSORT algorithm was used to evaluate the infiltration of immune cells in HT and NC samples. The transcript levels of verified genes from expanded samples were detected by quantitative real-time PCR.</p><p><strong>Results: </strong>A total of 1,401 differentially expressed genes (DEGs) were identified in HT patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these DEGs were predominantly enriched in immune-related pathways. Furthermore, 192 immune-related genes were identified in HT through the intersection of WGCNA modules, DEGs, and the IRGs. Among them, two upregulated genes ((Bruton's tyrosine kinase, BTK) and CD19) showed the potential diagnostic value for HT by using machine learning. The ROC curve analysis revealed that BTK had a higher diagnostic value than CD19 across two datasets. Intriguingly, only BTK expression was upregulated in the peripheral blood mononuclear cells of HT patients, and was significantly positively correlated with the serum levels of thyroid autoantibodies. Further studies confirmed a significant positive correlation between BTK and increased proportions of plasma cells in HT patients.</p><p><strong>Conclusion: </strong>This study identified BTK was significantly increased in HT patients, which might be the involved in the pathogenesis of HT by regulating plasma cells and represented a potential immune-related biomarker of HT.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"11"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of conditioned medium from miRNA-34a transfected gastric cancer-associated fibroblast on peripheral blood mononuclear cells.","authors":"Mozhgan Esmaili, Narjes Jafari, Fatemeh Ahmadzadeh, Seyed Mohammad Valizadeh Toosi, Saeid Abediankenari","doi":"10.1186/s12865-025-00688-6","DOIUrl":"10.1186/s12865-025-00688-6","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblast (CAF) cells play an important role in gastric malignancy. MiRNA dysregulation has been detected in CAF cells, which is related to the tumor progression ability of these cells. Therefore, this study aimed to evaluate the function of miRNA34a in CAF cells in gastric carcinoma.</p><p><strong>Method: </strong>We transiently transfected miRNA-34a mimic in CAF cells and examined the effect of the overexpressed miRNA on PD-L1 expression using real-time PCR. Next, we evaluated the role of transfected CAF-conditioned medium (CM) on the immune response and viability of gastric cancer cell lines.</p><p><strong>Results: </strong>We have shown that miRNA-34a significantly reduced PD-L1 expression in CAF cells (p < 0.05). However, the conditioned medium of transfected cells had no significant effect on the immune response. We also found that CM of miRNA-34a transfected CAF cells significantly suppressed gastric cancer cell line viability relative to the control group (P < 0.05).</p><p><strong>Conclusion: </strong>We indicated that CM of miRNA-34a transfected CAF can reduce gastric cancer cell line proliferation. Additionally, miRNA-34a in these cells may improve immune response via PD-L1 reduction. Thus, miRNA-34a could be a potential therapeutic agent in gastric cancer treatment.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"9"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC ImmunologyPub Date : 2025-02-19DOI: 10.1186/s12865-025-00687-7
Tariro D Chawana, Stephen R Walsh, Lynda Stranix-Chibanda, Zvavahera M Chirenje, Chenchen Yu, Lily Zhang, Kelly E Seaton, Jack Heptinstall, Lu Zhang, Carmen A Paez, Theresa Gamble, Shelly T Karuna, Philip Andrew, Brett Hanscom, Magdalena E Sobieszczyk, Srilatha Edupuganti, Cynthia L Gay, Sharon B Mannheimer, Christopher B Hurt, Kathryn E Stephenson, Laura L Polakowski, Hans Spiegel, Margaret Yacovone, Stephanie Regenold, Catherine Yen, Jane Ag Baumblatt, Lucio Gama, Dan H Barouch, Estelle Piwowar-Manning, Richard A Koup, Georgia D Tomaras, Ollivier Hyrien, Alison C Roxby, Yunda Huang
{"title":"Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.","authors":"Tariro D Chawana, Stephen R Walsh, Lynda Stranix-Chibanda, Zvavahera M Chirenje, Chenchen Yu, Lily Zhang, Kelly E Seaton, Jack Heptinstall, Lu Zhang, Carmen A Paez, Theresa Gamble, Shelly T Karuna, Philip Andrew, Brett Hanscom, Magdalena E Sobieszczyk, Srilatha Edupuganti, Cynthia L Gay, Sharon B Mannheimer, Christopher B Hurt, Kathryn E Stephenson, Laura L Polakowski, Hans Spiegel, Margaret Yacovone, Stephanie Regenold, Catherine Yen, Jane Ag Baumblatt, Lucio Gama, Dan H Barouch, Estelle Piwowar-Manning, Richard A Koup, Georgia D Tomaras, Ollivier Hyrien, Alison C Roxby, Yunda Huang","doi":"10.1186/s12865-025-00687-7","DOIUrl":"10.1186/s12865-025-00687-7","url":null,"abstract":"<p><p>VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prevent HIV acquisition in adults. However, differences in the pharmacokinetics (PK) of VRC07-523LS when administered alone vs. in combination with other mAbs have not been formally assessed. We performed a cross-protocol analysis of three clinical trials and included data from a total of 146 adults without HIV who received intravenous (n = 95) or subcutaneous (n = 51) VRC07-523LS, either alone ('single'; n = 100) or in combination with 1 or 2 other mAbs ('combined'; n = 46). We used an open, two-compartment population PK model to describe serum concentrations of VRC07-523LS over time, accounting for inter-individual variabilities. We compared individual-level PK parameters between the combined vs. single groups using the targeted maximum likelihood estimation method to adjust for participant characteristics. No significant differences were observed in clearance rate, inter-compartmental clearance, distribution half-life, or total VRC07-523LS exposure over time. However, for the combined group, mean central volume of distribution, peripheral volume of distribution, and elimination half-life were slightly greater, corresponding to slightly lower predicted concentrations early post-administration with high levels being maintained in both groups. These results suggest potential PK interactions between VRC07-523LS and other mAbs, but with small clinical impact in the context of HIV prevention. Our findings support coadministration of VRC07-523LS with other mAbs, and the use of the developed PK models to design future trials for HIV prevention.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"8"},"PeriodicalIF":2.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detecting the preoperative peripheral blood systemic immune-inflammation index (SII) as a tool for early diagnosis and prognosis of gallbladder cancer.","authors":"Feng Liu, Pengyu Yin, Baoping Jiao, Zhiyong Shi, Feifei Qiao, Jun Xu","doi":"10.1186/s12865-025-00683-x","DOIUrl":"10.1186/s12865-025-00683-x","url":null,"abstract":"<p><strong>Objective: </strong>Evidence indicates that the systemic immune-inflammation index (SII) correlates with poor prognosis in various solid tumors. This retrospective study aimed to evaluate the diagnostic and prognostic significance of preoperative SII combined with tumor markers for early detection and prognosis of gallbladder cancer (GBC).</p><p><strong>Methods: </strong>Preoperative SII levels and serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), and carbohydrate antigen 19 - 9 (CA19-9)] were measured in GBC patients. Correlations and diagnostic efficacy were analyzed using Spearman correlation and receiver operating characteristic (ROC) curve analyses. The relationship between SII and clinical data was analyzed, and cumulative survival rates of the two groups were compared. Independent risk factors for poor prognosis in GBC patients were assessed using Kaplan-Meier curves and Cox multivariate analysis.</p><p><strong>Results: </strong>Preoperative SII, CEA, CA125, and CA19-9 levels were significantly elevated in GBC patients compared to those with benign lesions. SII positively correlated with CEA, CA125, and CA19-9 levels (r = 0.434, 0.570, 0.614, respectively, all P < 0.001). The area under the ROC curve (AUC) for the combination of SII, CEA, CA125, and CA19-9 was 0.877 for early GBC diagnosis and 0.923 for predicting postoperative mortality, outperforming each marker individually. An SII threshold > 889.52 was predictive of postoperative death. High SII was associated with tumor size, differentiation, tumor-node-metastasis stage, lymph node metastasis, perineural invasion, surgical type, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and serum tumor marker levels. Kaplan-Meier analysis revealed poorer survival in the high SII group. Preoperative SII was identified as an IRF for poor prognosis in GBC patients.</p><p><strong>Conclusion: </strong>Preoperative SII correlates strongly with CEA, CA125, and CA19-9 levels. The combined use of SII and tumor markers offers high diagnostic value for early GBC detection and robust predictive value for postoperative mortality. Preoperative SII serves as an IRF for poor prognosis in GBC patients.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"7"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combining machine learning with external validation to explore necroptosis and immune response in moyamoya disease.","authors":"Yutong Liu, Kexin Yuan, Linru Zou, Chengxu Lei, Ruichen Xu, Shihao He, Yuanli Zhao","doi":"10.1186/s12865-025-00686-8","DOIUrl":"10.1186/s12865-025-00686-8","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a rare chronic vascular disease leads to cognitive impairment and stroke with its etiology unknown. The relationship between necroptosis or necroinflammation and MMD pathogenesis was poorly understood. Differentially expressed necroinflammation and necroptosis related genes (DE-NiNRGs) were selected based on the public gene expression data from Gene Expression Omnibus (GEO) and validated by our self-test data of MMD patients and control group. Functional enrichment analysis, PPI network and multi-factors regulation network construction of DE-NiNRGs were employed to discover the connections between these genes. DE-NiNRGs and immune cells correlation analysis provided evidence for the relationship between DE-NiNRGs and necroinflammation in MMD patients. We then established an MMD prediction model using support vector machine (SVM) and selected DE-NiNRGs as features. The DE-NiNRGs based MMD prediction model had excellent performance on test set with the area under the curve (AUC) higher than 0.9. Four genes, PTGER3, ANXA1, ID1, and IL1R1, that contributed significantly to the SVM model and passed the test of validation set are key genes in DE-NiNRGs. The upregulation of PTGER3 expression indicated that necroptosis and angiogenesis were promoted in MMD patients, whereas the downregulation of ANXA1 expression indicated that the migration and differentiation of immune cells are closely related to MMD pathogenesis. These findings provided new inspiration for our study of the immune-related pathogenesis and therapeutic targets of MMD.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"6"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC ImmunologyPub Date : 2025-02-10DOI: 10.1186/s12865-025-00684-w
Pan Jiang, Huai Huang, Mengshi Xie, Zilong Liu, Lijing Jiang, Hongyu Shi, Xiaodan Wu, Shengyu Hao, Shanqun Li
{"title":"Single-cell characterization of the immune heterogeneity of pulmonary hypertension identifies novel targets for immunotherapy.","authors":"Pan Jiang, Huai Huang, Mengshi Xie, Zilong Liu, Lijing Jiang, Hongyu Shi, Xiaodan Wu, Shengyu Hao, Shanqun Li","doi":"10.1186/s12865-025-00684-w","DOIUrl":"10.1186/s12865-025-00684-w","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a critical cardiopulmonary vascular disorder marked by the progressive elevation of pulmonary artery pressure, increased pulmonary vascular resistance, and eventual right heart failure. Research has shown that various immune cells play a significant role in the pathogenesis of PAH, both in patients diagnosed with the condition and in experimental models of PAH. Cell-cell communication is important for PAH progression and therapies, while the global cell landscape of intercellular signaling has not been elucidated.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE169471, GSE 210248, GSE228643 and GSE244781, and analyzed lung tissue samples across healthy controls and PAH patients. In total, approximately 124,561 cells were analyzed and a total 34 clusters were identified. We integrated the sequencing results of multiple samples and used an enhanced single-cell sequencing workflow to overcome the limitations of a single study.</p><p><strong>Results: </strong>In this study, we elucidated the functional characteristics and potential regulatory interactions of several cell subpopulations that have not been previously documented in similar research. We constructed a comprehensive landscape of cell communications at the single-cell resolution, which is expected to significantly advance the development of personalized diagnostic and therapeutic strategies for PAH. We demonstrated the transcriptomic features of different cell types in PAH patients. We presented an in-depth analysis of T cell subsets, myeloid cell heterogeneity and a comprehensive analysis of SMCs and FBs subsets in PAH. T cell heterogeneity and functional dynamics were exhibited in PAH, which suggests that targeting cytotoxic regulation may be a potential therapeutic strategy. Significant changes and potential functions of myeloid cell subsets in PAH patients and we especially focused on GPNMB<sup>+</sup> macrophages. In addition, CellChat and NicheNet analyses reveal altered intercellular communication and dys-regulated signaling pathways in PAH progression. The enhanced MIF and IL-1 signaling suggests that the induced inflammatory response in PAH is greatly driven.</p><p><strong>Conclusions: </strong>We systematically explored the immune heterogeneity and population and target cells in PAH, which may be valuable for developing new and precise therapies.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"5"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC ImmunologyPub Date : 2025-01-23DOI: 10.1186/s12865-025-00682-y
Miro Saarela, Essi Parviainen, Ana Lleo, Luca di Tommaso, Hanna Raunio, Krista Kankaanranta, Katri Vuopala, Aino Rönkä, Sini Nurmenniemi, Raija Kallio, Arja Jukkola, Katri S Selander
{"title":"Increased PD-1 expression in livers associated with PD-1-antibody-induced hepatotoxicity.","authors":"Miro Saarela, Essi Parviainen, Ana Lleo, Luca di Tommaso, Hanna Raunio, Krista Kankaanranta, Katri Vuopala, Aino Rönkä, Sini Nurmenniemi, Raija Kallio, Arja Jukkola, Katri S Selander","doi":"10.1186/s12865-025-00682-y","DOIUrl":"10.1186/s12865-025-00682-y","url":null,"abstract":"<p><p>Vanishing bile duct syndrome (VBDS) is a serious drug induced liver injury characterized by chronic cholestasis and loss of intrahepatic bile ducts. VBDS has been reported also following checkpoint inhibitor treatment. We compared CD3 + , CD4 + , CD8 + , CD20 + , CD57 + , PD-1 + and PD-L1 + lymphocyte infiltrates in liver biopsies of patients that encountered VBDS (n = 2) or hepatotoxicity (n = 3) after pembrolizumab (n = 4) or nivolumab (n = 1) treatment with samples from normal liver (n = 10), non-alcohol steatohepatitis (NASH, n = 10), primary biliary cholangitis (PBC, n = 10) or pembrolizumab-treated patients without adverse events (n = 2). Notably, none of the cancer patients had primary nor metastatic liver tumors. We also studied direct growth effects of pembrolizumab on primary human intrahepatic biliary epithelial cells (HIBEpiC) in vitro. Liver sections of all checkpoint inhibitor- treated patients exhibited significantly higher CD3 + infiltration than normal livers, and significantly higher PD-L1 + , CD4 + and CD8 + infiltration, than other groups. PD-1 + infiltration was significantly increased in livers of patients with severe hepatic adverse event. CD57 + infiltration was similar in normal livers, NASH- and PBC groups, but highly increased in the checkpoint inhibitor-treated patients. Immune cell infiltrates were similar between NASH and normal livers. PBC samples had significantly higher CD3 + , CD4 + , CD8 + and CD20 + infiltrates than normal livers. HIBEpiC express PD-L1 but pembrolizumab did not affect their viability in vitro. Our findings suggest that VBDS is not due to direct cytotoxicity of checkpoint inhibitors and that the immunological attack against livers induced by these drugs is different from other cholestatic liver conditions.Biological insight: Checkpoint inhibitors upregulate PD-1 and PD-L1, as well as cytotoxic CD57 + cells in the non-cancerous liver tissues and this may be associated with checkpoint inhibitor-induced hepatotoxicity.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"4"},"PeriodicalIF":2.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC ImmunologyPub Date : 2025-01-14DOI: 10.1186/s12865-024-00679-z
Song I Lee, Na Young Kim, Chaeuk Chung, Dongil Park, Da Hyun Kang, Duk Ki Kim, Min-Kyung Yeo, Pureum Sun, Jeong Eun Lee
{"title":"IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis.","authors":"Song I Lee, Na Young Kim, Chaeuk Chung, Dongil Park, Da Hyun Kang, Duk Ki Kim, Min-Kyung Yeo, Pureum Sun, Jeong Eun Lee","doi":"10.1186/s12865-024-00679-z","DOIUrl":"10.1186/s12865-024-00679-z","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of simultaneous blockade of IL-6 and PD-1 in a murine sepsis model are not well understood.</p><p><strong>Results: </strong>In this study, sepsis was induced in male C57BL/6 mice through cecal ligation and puncture (CLP). IL-6 blockade, PD-1 blockade, or combination of both was administered 24 h after CLP. Peripheral blood count, cytokine level, lymphocyte apoptosis in the spleen, neutrophil infiltration in the lungs and liver, and survival rate were measured. The mortality rate of the IL-6/PD-1 group was lower, though not statistically significant (p = 0.164), than that of CLP mice (75.0% vs. 91.7%). The IL-6/PD-1 group had lower neutrophil percentage and platelet count compared with the CLP group; no significant difference was observed in other cytokine levels. The IL-6/PD-1 group also showed reduced T lymphocyte apoptosis in the spleen and decreased neutrophil infiltration in the liver and lungs.</p><p><strong>Conclusions: </strong>IL-6/PD-1 dual blockade reduces neutrophil infiltration, lymphocyte apoptosis, and bacterial burden while preserving tissue integrity in sepsis. Although the improvement in survival was not statistically significant, these findings highlight its potential as a therapeutic approach in sepsis.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC ImmunologyPub Date : 2025-01-10DOI: 10.1186/s12865-025-00681-z
Yu Bai, Jun Ding, Liuyang He, Zhichao Zhu, Jie Pan, Chunjian Qi
{"title":"β-Glucan induced plasma B cells differentiation to enhance antitumor immune responses by Dectin-1.","authors":"Yu Bai, Jun Ding, Liuyang He, Zhichao Zhu, Jie Pan, Chunjian Qi","doi":"10.1186/s12865-025-00681-z","DOIUrl":"10.1186/s12865-025-00681-z","url":null,"abstract":"<p><strong>Background: </strong>B lymphocytes, essential in cellular immunity as antigen-presenting cells and in humoral immunity as major effector cells, play a crucial role in the antitumor response. Our previous work has shown β-glucan enhanced immunoglobulins (Ig) secretion. But the specific mechanisms of B-cell activation with β-glucan are poorly understood. Here, we took advantage of β-glucan to improve the antitumor immune response of B cells.</p><p><strong>Results: </strong>In vitro experiments demonstrate that β-glucan enhance the differentiation of B220<sup>lo</sup> CD138<sup>+</sup> B cells, up-regulate co-stimulatory molecules, and increase the production of cytokines and Ig in response to various antigens. Using the Dectin-1 knockout mice, we revealed that β-glucan modulate B cell immune responses dependent on Dectin-1 receptor. In mouse models of Lewis lung cancer (LLC) tumors, combining β-glucan with programmed death-1(PD-1) blocking antibodies led to increase recruitment of CD19<sup>+</sup> B cells in the tumor microenvironment (TME), higher numbers of germinal centers B cells (GC B) in the spleen and draining lymph node (DLN), elevate Ig production, and delay tumor progression.</p><p><strong>Conclusions: </strong>These findings reveal that β-glucan can serve as a potent adjuvant to modulate B cell immune responses in a Dectin-1 dependent manner and improve immune checkpoint blockade (ICB) therapy in antitumor.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"2"},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep analysis of the major histocompatibility complex genetic associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS.","authors":"Myriam Rahmouni, Sigrid Le Clerc, Jean-Louis Spadoni, Taoufik Labib, Maxime Tison, Raissa Medina-Santos, Armand Bensussan, Ryad Tamouza, Jean-François Deleuze, Jean-François Zagury","doi":"10.1186/s12865-024-00680-6","DOIUrl":"https://doi.org/10.1186/s12865-024-00680-6","url":null,"abstract":"<p><strong>Introduction: </strong>We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).</p><p><strong>Methods: </strong>A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.</p><p><strong>Results: </strong>Two thousand six hundred twenty-six SNPs were associated with EC (p<5.10-8), all located within the Major Histocompatibility Complex (MHC) region. Stepwise regression analysis narrowed this list to 17 SNPs. In parallel, 22 HLA class I and II alleles were associated with EC. Through meticulous mapping of the LD between all identified signals and employing reciprocal covariate analyses, we delineated a final set of 6 independent SNPs and 3 HLA class I gene alleles that accounted for most of the associations observed with EC. Our study revealed the presence of cumulative haploblock effects (SNP rs9264942 contributing to the HLA-B*57:01 effect) and that several HLA allele associations were in fact caused by SNPs in linkage disequilibrium (LD). Upon investigating SNPs in LD with the selected 6 SNPs and 3 HLA class I alleles for their impact on protein function (either damaging or differential expression), we identified several compelling mechanisms potentially explaining EC among which: a multi-action mechanism of HLA-B*57:01 involving MICA mutations and MICB differential expression overcoming the HIV-1 blockade of NK cell response, and overexpression of ZBTB12 with a possible anti-HIV-1 effect through HERV-K interference; a deleterious mutation in PPP1R18 favoring viral budding associated with rs1233396.</p><p><strong>Conclusion: </strong>Our results show that MHC influence on EC likely extends beyond traditional HLA class I or class II allele associations, encompassing other MHC SNPs with various biological impacts. They point to the key role of NK cells in preventing HIV-1 infection. Our analysis shows that HLA-B*57:01 is indeed associated with partially functional MICA/MICB proteins which could also explain this marker's involvement in other diseases such as psoriasis. More broadly, our findings suggest that within any HLA class I and II association in diseases, there may exist distinct causal SNPs within this crucial, gene-rich, and LD-rich MHC region.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}