Molecular immunology最新文献_第8页

The mechanism of SMAD4/ERK pathway in regulating Th17/Treg cell differentiation leading to olfactory dysfunction in chronic rhinosinusitis SMAD4/ERK通路调控Th17/Treg细胞分化导致慢性鼻窦炎嗅觉功能障碍的机制

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-25 DOI: 10.1016/j.molimm.2025.09.006

Shouming Cao , Yan Niu , Jinmei Ning , Nannan Wen , Rui Chen , Haiying Wu

{"title":"The mechanism of SMAD4/ERK pathway in regulating Th17/Treg cell differentiation leading to olfactory dysfunction in chronic rhinosinusitis","authors":"Shouming Cao , Yan Niu , Jinmei Ning , Nannan Wen , Rui Chen , Haiying Wu","doi":"10.1016/j.molimm.2025.09.006","DOIUrl":"10.1016/j.molimm.2025.09.006","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis (CRS) is characterized by a high recurrence rate within five years post-surgery, posing a persistent challenge for otolaryngologists globally. Recent research has underscored the pivotal role of the Th17/Treg cell balance in the pathogenesis of CRS. This study aims to investigate the alterations in the Th17/Treg cell balance in CRS and elucidate the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>CRS model was established to assess the levels of inflammatory cytokines, olfactory marker protein expression, SMAD4 expression, and ERK1/2 phosphorylation. We then overexpressed SMAD4 or treated CRS mice with ERK1/2 inhibitors, measuring the impact on Th17/Treg marker expression. Moreover, the influence of the SMAD4/ERK signaling axis on the Th17/Treg balance within the CD4 + T cell population was investigated.</div></div><div><h3>Results</h3><div>CRS mice exhibited significantly reduced olfactory marker protein and SMAD4 expression, alongside increased ERK1/2 phosphorylation. Histological analysis revealed an increased infiltration of eosinophils. Of particular note, the expression of Treg markers was markedly decreased, while Th17 marker expression exhibited a corresponding increase, suggesting a potential shift in the Th17/Treg balance. Interventions involving SMAD4 overexpression or ERK1/2 inhibition led to a reduction in eosinophil infiltration and successfully reversed the aberrant expression patterns of the aforementioned markers. Furthermore, SMAD4 knockdown resulted in a decreased proportion of Treg cells and an increased proportion of Th17 cells. This alteration in the Th17/Treg balance was effectively counteracted by ERK inhibitor.</div></div><div><h3>Conclusions</h3><div>The deletion of SMAD4 regulates the differentiation of Th17/Treg cells via ERK1/2 phosphorylation, thereby exacerbating the olfactory dysfunction of CRS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 142-151"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154974","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

TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma TNF-α和IFN-γ调节原发性纵隔b细胞淋巴瘤的免疫应答逃避。

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-06 DOI: 10.1016/j.molimm.2025.09.009

Paula Gršković , Valentino Mihalić , Anja Krstulović , Peter Möller , Suzana Hančić , Slavko Gašparov , Petra Korać

{"title":"TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma","authors":"Paula Gršković , Valentino Mihalić , Anja Krstulović , Peter Möller , Suzana Hančić , Slavko Gašparov , Petra Korać","doi":"10.1016/j.molimm.2025.09.009","DOIUrl":"10.1016/j.molimm.2025.09.009","url":null,"abstract":"<div><h3>Objectives</h3><div>Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL). PMBCL often contains aberrations of genes involved in the immune response such as <em>cREL</em> and <em>PD-L1</em>, whose expression is also influenced by cytokines TNF-α and IFN-γ.</div></div><div><h3>Methods</h3><div>In this study, cell lines Farage, U2940, MedB-1 and Karpas1106p were used as PMBCL models and treated with different concentrations of TNF-α and IFN-γ over 24 and 48 h, followed by the quantification of <em>cREL</em>, <em>CXCL10</em> and <em>PD-L1</em> expression. Additionally, the expression of <em>TNF-α</em>, <em>IFN-γ</em>, <em>cREL</em>, <em>CXCL10</em>, <em>CXCR3</em>, <em>PD-L1</em> and <em>PD-1</em> genes was compared between PMBCL tissue samples and B-cell and T-cell rich zones of non-tumour tonsils.</div></div><div><h3>Results</h3><div>Prolonged exposure to TNF-α increased <em>cREL</em> expression, while IFN-γ strongly induced <em>CXCL10</em> expression. The change in the expression of <em>PD-L1</em> in response to the treatments differed across various cell lines. There was no statistically significant difference in the expression of the target genes between tumour and non-tumour patient tissue samples.</div></div><div><h3>Conclusions</h3><div>the obtained results suggest that the immune checkpoints in PMBCL cells are affected by both their genetic profile and tumour microenvironment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 178-187"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244784","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

Drice negatively regulates cellular and humoral immunity of Drosophila melanogaster price负向调节果蝇的细胞免疫和体液免疫

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-06 DOI: 10.1016/j.molimm.2025.08.020

Priyanka Jaiswal, Madhu G. Tapadia

{"title":"Drice negatively regulates cellular and humoral immunity of Drosophila melanogaster","authors":"Priyanka Jaiswal, Madhu G. Tapadia","doi":"10.1016/j.molimm.2025.08.020","DOIUrl":"10.1016/j.molimm.2025.08.020","url":null,"abstract":"<div><div>The innate immune response is a double-edged sword in insects, comprising the humoral and cellular mechanisms to fight and eliminate pathogens. The humoral response is achieved by the production of antimicrobial peptides, which are secreted in the hemolymph. The cellular responses are mediated by phagocytosis, encapsulation and melanization. Though the fat bodies are the primary immune tissues in <em>Drosophila,</em> secreting AMPs, the Malpighian tubules are also autonomous immune organs that constitutively secrete AMPs at basal levels, which increases after infection. Here we provide evidence to show that the caspase 3 homolog in <em>Drosophila</em>, Drice, negatively regulates both, cellular as well as humoral immunity. Depletion of Drice leads to the increased expression of transcription factor Relish, which enhances the expression of certain AMPs regulated by the IMD pathway. In the absence of Drice, both the Ecdysone receptor- B1 and Broad-core (Br-C) are also upregulated which are upstream regulators of the IMD pathway. The increase in crystal cells clearly indicates Drice to be a negative regulator of this form of cellular immunity. Collectively our findings suggest the role of Drice in the immune regulation of <em>Drosophila melanogaster</em>, and these results will add to the growing understanding of diverse roles of caspases in immune regulation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 61-65"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004623","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

SNHG16-loaded extracellular vesicles from hypoxic NSCLC cells drive M2 macrophage polarization to enhance cancer aggressiveness 缺氧NSCLC细胞中装载snhg16的细胞外囊泡驱动M2巨噬细胞极化以增强肿瘤侵袭性

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-08 DOI: 10.1016/j.molimm.2025.08.022

Yanshen Hou , Ximing Li , Lingfei Zeng , Yuan Zhang

{"title":"SNHG16-loaded extracellular vesicles from hypoxic NSCLC cells drive M2 macrophage polarization to enhance cancer aggressiveness","authors":"Yanshen Hou , Ximing Li , Lingfei Zeng , Yuan Zhang","doi":"10.1016/j.molimm.2025.08.022","DOIUrl":"10.1016/j.molimm.2025.08.022","url":null,"abstract":"<div><div>Hypoxia plays a critical role in regulating the progression of non-small cell lung cancer (NSCLC) by modulating the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs), important components of TIME, can be regulated by hypoxic conditions. Unfortunately, the molecular mechanisms by which hypoxia regulates TAMs in TIME to affect NSCLC progression has not been fully delineated. The present study evidenced that hypoxia-stimulated NSCLC cells secreted extracellular vesicles (EVs) were featured with highly expressed small nucleolar RNA host gene 16 (SNHG16), and SNHG16-containing EVs (SNHG16-EVs) synergistically promoted cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties in NSCLC cells, and induced M2-polarization of macrophages in THP-1 cells through delivering SNHG16. Notably, M2-polarized macrophages were capable of enhancing cancer aggressiveness in NSCLC cells through secreting tumor-initiating cytokines, including interleukin-10 (IL-10), transforming growth factor β (TGF-β), and vascular endothelial-derived growth factor (VEGF). Mechanistically, it was found that SNHG16 sponged miR-132–3p to positively regulate its downstream target, kinesin family member 5 A (KIF5A), via a competing endogenous RNA (ceRNA) mechanism-dependent manner. Rescue experiments confirmed that SNHG16-EVs induced NSCLC progression and M2 polarization of THP-1 cells were all reversed by overexpressing miR-132–3p and silencing KIF5A. Collectively, hypoxia-stimulated NSCLC cells transferred SNHG16-containing EVs to promote cancer aggressiveness and M2-polarized macrophages in NSCLC through modulating the downstream miR-132–3p/KIF5A axis, and this study verified that targeting SNHG16-EVs may be a novel strategy to hamper NSCLC progression via modulating TME.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 66-79"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010908","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

Role of efferocytosis in liver transplantation via hepatic macrophage 肝巨噬细胞在肝移植中的作用。

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-14 DOI: 10.1016/j.molimm.2025.10.003

Minjie Zhao , Xuesong Xu , Haiyang Peng , Changlin Tang , Jiefu Luo , Junyan Liu , Zuojin Liu , Jianping Gong , Junhua Gong , Jinzheng Li

{"title":"Role of efferocytosis in liver transplantation via hepatic macrophage","authors":"Minjie Zhao , Xuesong Xu , Haiyang Peng , Changlin Tang , Jiefu Luo , Junyan Liu , Zuojin Liu , Jianping Gong , Junhua Gong , Jinzheng Li","doi":"10.1016/j.molimm.2025.10.003","DOIUrl":"10.1016/j.molimm.2025.10.003","url":null,"abstract":"<div><div>Liver transplantation has undergone progressive advancements since the 1960s, with optimized surgical techniques and improved outcomes resulting from standardized procedures and therapeutic regimens. However, postoperative complications—such as ischemia-reperfusion injury, acute rejection, hepatocellular carcinoma recurrence, and biliary injury—continue to significantly affect both survival rates and quality of life in liver transplant recipients. Efferocytosis, the phagocytic clearance of apoptotic cells, plays a critical role in preventing necrosis-induced inflammation and promoting tissue resolution and repair. Accumulating evidence suggests that impaired efferocytosis is associated with several complications following liver transplantation. Although multiple hepatic cell types participate in efferocytosis, macrophages—notably Kupffer cells and monocyte-derived macrophages—are the primary mediators responsible for clearing apoptotic cells in the liver. Nevertheless, significant gaps remain in our understanding of how hepatic macrophages perform efferocytosis and whether defects in this process within donor-derived macrophages exacerbate post-transplant complications. This review provides a comprehensive discussion of efferocytosis, with a focus on its impact on liver transplantation-related complications. Furthermore, we explore the potential of targeting efferocytosis as a novel therapeutic strategy in liver transplantation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 221-228"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302162","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

Therapeutic targeting of neuroinflammation in sphingolipidosis 鞘脂病神经炎症的靶向治疗

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-23 DOI: 10.1016/j.molimm.2025.09.005

Ebru Ada , Volkan Seyrantepe

{"title":"Therapeutic targeting of neuroinflammation in sphingolipidosis","authors":"Ebru Ada , Volkan Seyrantepe","doi":"10.1016/j.molimm.2025.09.005","DOIUrl":"10.1016/j.molimm.2025.09.005","url":null,"abstract":"<div><div>Lysosomal storage diseases (LSDs) are a class of hereditary metabolic disorders primarily caused by lysosomal enzyme defects, leading to the accumulation of undegraded substrates. Sphingolipidoses, a subset of LSDs, are primarily associated with profound involvement of the central nervous system (CNS), characterized by progressive neurodegeneration due to massive sphingolipid accumulation. A common pathological feature among many CNS-involved LSDs is the early activation of microglia and astrocytes, which often precedes and predicts regions of subsequent neuronal loss. The extent to which neuroinflammation disrupts CNS homeostasis appears to be determined by its onset, magnitude, and duration. Although neuroinflammatory processes are increasingly recognized as critical contributors to disease progression in sphingolipidoses, the molecular mechanisms underlying glial activation and the initiation of inflammatory cascades remain incompletely understood. Therefore, mouse models of sphingolipidoses have been instrumental in elucidating these pathogenic processes and provide valuable platforms for evaluating therapeutic strategies. This review critically examines the role of neuroinflammation in sphingolipidoses, summarizes insights derived from pre-clinical models, and discusses the therapeutic potential of anti-inflammatory interventions to mitigate CNS pathology and improve clinical outcomes.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 121-133"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118646","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 metabolic regulation of tumor-associated macrophage reprogramming 肿瘤相关巨噬细胞重编程的代谢调控。

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-14 DOI: 10.1016/j.molimm.2025.10.006

Hao Fan , Dongxiao Lu , Xianyong Yin , Hao Sun , Zhihai Wang , Haohan Sun , Xiangyin Liu , Yuming Li , Zijian Zhou , Liang Chen , Yinyan Wang , Tao Xin

{"title":"The metabolic regulation of tumor-associated macrophage reprogramming","authors":"Hao Fan , Dongxiao Lu , Xianyong Yin , Hao Sun , Zhihai Wang , Haohan Sun , Xiangyin Liu , Yuming Li , Zijian Zhou , Liang Chen , Yinyan Wang , Tao Xin","doi":"10.1016/j.molimm.2025.10.006","DOIUrl":"10.1016/j.molimm.2025.10.006","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) are an essential component of the immune cells that infiltrate the tumor microenvironment (TME) and exhibit immunosuppressive functions. These macrophages exhibit significant phenotypic plasticity and heterogeneity, highlighting their capacity to adapt to various environmental signals. This adaptability facilitates polarization shifts between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. As tumors proliferate and metastasize, the TME progressively transforms into an immunosuppressive environment. Consequently, TAMs undergo metabolic reprogramming in pathways such as glucose, lipid, and amino acid metabolism, among others, which ultimately drive the establishment of an immunosuppressive phenotype. While TAMs do not strictly conform to the M1 and M2 classifications, they often exhibit characteristics resembling M2 macrophages, thereby promoting tumor growth via immunosuppression. This review aims to elucidate the metabolic reprogramming of TAMs and investigate how they maintain their immunosuppressive phenotype, highlighting potential avenues for metabolic therapies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 198-209"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302076","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

GATA1 promotes TGF-β1-induced epithelial-mesenchymal transition by regulating GSDMB in human bronchial epithelial cells GATA1通过调节人支气管上皮细胞GSDMB促进TGF-β1诱导的上皮-间质转化。

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-14 DOI: 10.1016/j.molimm.2025.10.004

Jiao-jiao Li , Jia-he Chen , Yue Yuan , Ling Li , Chen Zhou , Hu Chen , Jia Geng , Qian Cao , Rui Jin

{"title":"GATA1 promotes TGF-β1-induced epithelial-mesenchymal transition by regulating GSDMB in human bronchial epithelial cells","authors":"Jiao-jiao Li , Jia-he Chen , Yue Yuan , Ling Li , Chen Zhou , Hu Chen , Jia Geng , Qian Cao , Rui Jin","doi":"10.1016/j.molimm.2025.10.004","DOIUrl":"10.1016/j.molimm.2025.10.004","url":null,"abstract":"<div><div>Asthma is a common inflammatory airway disorder characterized by recurrent cough, chest tightness, and dyspnea. The repeated inflammation of bronchial epithelial cells leading to epithelial-mesenchymal transition is believed to play a pivotal role in airway remodeling associated with asthma. Gasdermin B (GSDMB), a member of the gasdermin family of structurally related proteins, has been identified as having a strong association with asthma. However, the precise role of GSDMB in asthma pathophysiology remains ambiguous. This study aimed to elucidate the biological function of GSDMB in asthma and its upstream regulatory mechanisms. Our findings demonstrated that GSDMB expression was also increased in human bronchial epithelial cells stimulated with transforming growth factor-β1 (TGF-β1). Overexpression of GSDMB resulted in an upregulation of intermediate mesenchymal markers following TGF-β1 treatment, thereby facilitating epithelial-mesenchymal transition (EMT) processes. Furthermore, GSDMB enhanced both proliferation and migration capacity in TGF-β1-treated Beas-2B cells. Notably, the transcription factor GATA1 was found to bind to the promoter region of GSDMB and facilitate its expression levels. These results indicate that the transcriptional axis involving GATA1/GSDMB exerts functions promoting EMT along with enhancing cellular proliferation and migration within TGF-β1-stimulated bronchial epithelial cells; suggesting that targeting GSDMB may represent a viable therapeutic strategy for managing asthma.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 229-239"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302134","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

Study on the adjuvant activity and mechanism of action of a novel Monophosphoryl Lipid A 新型单磷酰脂质a的佐剂活性及作用机制研究

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-03 DOI: 10.1016/j.molimm.2025.08.019

Lichun Zhao, Peixin Shi, Yujiao Zhang, Mingxuan Zhang, Na Han, Zhihui Liu, Sikai Li, Jun Yin, Jianxiu Zhai

{"title":"Study on the adjuvant activity and mechanism of action of a novel Monophosphoryl Lipid A","authors":"Lichun Zhao, Peixin Shi, Yujiao Zhang, Mingxuan Zhang, Na Han, Zhihui Liu, Sikai Li, Jun Yin, Jianxiu Zhai","doi":"10.1016/j.molimm.2025.08.019","DOIUrl":"10.1016/j.molimm.2025.08.019","url":null,"abstract":"<div><div>In order to develop a novel vaccine adjuvant that is highly efficient, cost-effective, and suitable for widespread application, this study employed synthetic biology techniques to produce a new type of <em>Escherichia coli</em> monophosphate lipid A (N-MPL). Specifically, the phosphate group attached to the C-1 position was removed, and a hydroxyl group was introduced into the 3′-secondary fatty acid chain of the original lipid A structure. This modification aimed to reduce toxicity while enhancing water solubility. Two formulations of N-MPL were prepared and their immunological and adjuvant activities were evaluated. Results demonstrated that both formulations could promote the proliferation of immune cells and the maturation of bone marrow-derived dendritic cells (BMDCs). In an adjuvant immunization experiment using H1N1 vaccine in ICR mice, N-MPL exhibited superior adjuvant effects compared to aluminum adjuvants and commercially available Monophosphoryl Lipid A (Synthetic) (PHAD™). Through comprehensive analysis of splenic lymphocytes, antibodies, cytokines, and immune factors in immunized mice, it was discovered for the first time that different formulations of N-MPL adjuvants could regulate cellular and humoral immunity, albeit with distinct foci of induced immune responses. The oil-in-water formulation of N-MPL primarily induced cellular immune responses in mice, whereas the aqueous solution formulation predominantly elicited humoral immune responses. Mechanistic studies revealed that N-MPL regulates the Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway. Overall, the novel N-MPL adjuvant exhibits high efficiency and low cost, demonstrating significant potential for vaccine adjuvant development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 28-47"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933540","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

Antibody preparation and immunological analysis of RBD from the SARS-CoV-2 Omicron BF.7 variant SARS-CoV-2 Omicron BF.7变异RBD抗体制备及免疫学分析

IF 3 3区医学

Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-07 DOI: 10.1016/j.molimm.2025.09.008

Quansheng Wang , Chenyi Wang , Zhicheng Zhang , Siyu Fan , Ping Lei , Shiguo Liu , Mingzhi Li , Keyi Wang , Yanni Zhang , Lumei Kang , Shiqi Weng , Lingbao Kong , Ting Wang

{"title":"Antibody preparation and immunological analysis of RBD from the SARS-CoV-2 Omicron BF.7 variant","authors":"Quansheng Wang , Chenyi Wang , Zhicheng Zhang , Siyu Fan , Ping Lei , Shiguo Liu , Mingzhi Li , Keyi Wang , Yanni Zhang , Lumei Kang , Shiqi Weng , Lingbao Kong , Ting Wang","doi":"10.1016/j.molimm.2025.09.008","DOIUrl":"10.1016/j.molimm.2025.09.008","url":null,"abstract":"<div><div>The SARS-CoV-2 spike protein facilitates target recognition, cellular entry, and viral infection, leading to varying degrees of COVID-19 severity. Amino acid site mutations in the S protein RBD region can enhance the spread and immune evasion of the SARS-CoV-2 Omicron variant. The study aimed to construct a prokaryotic expression vector for the S protein RBD of the SARS-CoV-2 Omicron BF.7 variant strain. <em>Escherichia coli</em> was used to express the RBD protein, and a polyclonal antibody was generated to investigate the immunological functions of the Omicron (BF.7) RBD. Optimization of expression conditions in <em>Escherichia coli</em> was conducted to achieve stable expression of pET-28a-BF.7-RBD, including induced temperature, induced time, and IPTG concentration. Serum antibody titers in RBD-immunized mice reached up to 1: 204800 as determined by indirect enzyme-linked immunosorbent assay. The polyclonal antibody could detect prokaryotic and eukaryotic RBD proteins, as well as commercial RBD proteins, and splenocytes were found to produce high levels of IFN-γ. This study successfully demonstrated the production of a large quantity of RBD protein with strong immunogenicity in <em>E. coli</em>, eliciting robust humoral and cellular immune responses in mice. The generation of high-potency polyclonal antibodies provides valuable insights for further research on the biological functions of the RBD protein, detection of Omicron variants, and vaccine development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 188-197"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251967","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