Immunology最新文献_第5页

Loss of ALK3 Ameliorates Acute but Aggravates Chronic Lung Inflammation In Vivo 体内丧失ALK3可改善急性但加重慢性肺炎症。

IF 5 3区医学

Immunology Pub Date : 2025-06-02 DOI: 10.1111/imm.13957

Mathias Hochgerner, Yamei Jiang, Shenfei Sun, Fujing Huang, Leigh M. Marsh, Xinhua Lin, Xiaofang Tang

{"title":"Loss of ALK3 Ameliorates Acute but Aggravates Chronic Lung Inflammation In Vivo","authors":"Mathias Hochgerner, Yamei Jiang, Shenfei Sun, Fujing Huang, Leigh M. Marsh, Xinhua Lin, Xiaofang Tang","doi":"10.1111/imm.13957","DOIUrl":"10.1111/imm.13957","url":null,"abstract":"<div>\u0000 \u0000 ALK3 (BMPR1a) is a type-1 receptor of the TGF-β receptor superfamily. It translates signals mainly from bone morphogenetic proteins, but also from TGF-β1. Previously, we showed that specific deletion of ALK3 in antigen-presenting cells (APCs) led to increased inflammation in the skin. It is unknown whether the regulation of ALK3 in APCs is specific to the skin or generally involved in multiple tissues. Therefore, we investigated the role of ALK3 in APCs in the lung. We used mice with a specific deletion of ALK3 under the CD11c promoter as well as pharmacological blockade of ALK3-signalling with DMH-1 in vivo in Bleomycin- and LPS-induced lung inflammation, as well as follow-up in vitro experiments. Lung inflammation was analysed via histology, flow cytometry and single-cell-RNA-sequencing. Deletion or blockade of ALK3 aggravated Bleomycin-induced and long-term LPS-induced lung inflammation. Interestingly, acute LPS-induced lung inflammation was ameliorated. ALK3 blockade did not reduce recruitment of immune cells to the lung but changed gene expression in neutrophils, downregulating inflammation-associated genes. In vitro, DMH-1 did not directly affect neutrophils but did affect DCs, macrophages and AT-2 cells. The aggravation of longer-lasting lung inflammation matches our previous data from the skin, down to reduced numbers of TREG. Unexpectedly, that same loss/blockade of ALK3 ameliorates acute lung inflammation. Our results suggest that ALK3 is an important receptor in APCs, enhancing their ability to activate a fast, neutrophilic inflammation as well as to counteract longer-lasting inflammations. Thus, ALK3 has (at least) two different functions at different stages of inflammation. With deeper understanding, ALK3 could be an important target for modulating acute and chronic lung inflammation.\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 2","pages":"224-236"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208450","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

PI3Kγ in Tumour Inflammation: Bridging Immune Response and Cancer Progression—A Mini-Review PI3Kγ在肿瘤炎症中的作用：桥接免疫反应和癌症进展

IF 5 3区医学

Immunology Pub Date : 2025-05-28 DOI: 10.1111/imm.13959

Anghesom Ghebremedhin, Judith A. Varner

引用次数: 0

Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis 利用多重成像分析描绘人类生发中心免疫景观。

IF 5 3区医学

Immunology Pub Date : 2025-05-27 DOI: 10.1111/imm.13955

Spiros Georgakis, Michail Orfanakis, Craig Fenwick, Cloe Brenna, Simon Burgermeister, Helen Lindsay, Giuliana Xavier de Medeiros, Fernanda Romano Bruno, Susan Pereira Ribeiro, Raphael Gottardo, Giuseppe Pantaleo, Constantinos Petrovas

{"title":"Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis","authors":"Spiros Georgakis, Michail Orfanakis, Craig Fenwick, Cloe Brenna, Simon Burgermeister, Helen Lindsay, Giuliana Xavier de Medeiros, Fernanda Romano Bruno, Susan Pereira Ribeiro, Raphael Gottardo, Giuseppe Pantaleo, Constantinos Petrovas","doi":"10.1111/imm.13955","DOIUrl":"10.1111/imm.13955","url":null,"abstract":"Given the role of follicular immune dynamics, especially the germinal centre, for the development of pathogen-specific antibodies, their in situ characterisation is of great importance. We have developed a multiplex immunofluorescence imaging pipeline that allows the analysis of human follicular adaptive and innate immune cell subsets. Our data revealed the in situ phenotypic heterogeneity and differential localisation of follicular helper CD4 T (TFH) cell subsets across follicular areas in tonsils and reactive lymph nodes (LNs). Cell clustering analysis identified specific TFH subsets with differential prevalence between tonsils and LNs. Further, a multiplex RNAscope/protein imaging assay revealed the functional heterogeneity of TFH cells. No significant differences in follicular innate immune cell densities were found between tonsils and LNs. In conclusion, we present a combinatory experimental approach that provides a comprehensive analysis of human follicular and/or germinal centre immune dynamics and could be used to further understand the pathogenesis of diseases such as HIV and lymphomas.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 1","pages":"87-104"},"PeriodicalIF":5.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13955","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150371","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

Nck1 Regulates Glucose Metabolism in Primary Human T Cells Nck1调控原代人T细胞的糖代谢

IF 5 3区医学

Immunology Pub Date : 2025-05-27 DOI: 10.1111/imm.13950

Araya Rattanasri, Pussadee Paensuwan, Wolfgang W. W. A. Schamel, Sutatip Pongcharoen, Jatuporn Ngoenkam

{"title":"Nck1 Regulates Glucose Metabolism in Primary Human T Cells","authors":"Araya Rattanasri, Pussadee Paensuwan, Wolfgang W. W. A. Schamel, Sutatip Pongcharoen, Jatuporn Ngoenkam","doi":"10.1111/imm.13950","DOIUrl":"10.1111/imm.13950","url":null,"abstract":"<div>\u0000 \u0000 Non-catalytic region of tyrosine kinase 1 (Nck1) is an adaptor protein found in many cell types and plays several functions. In T cells, Nck1 is functionally associated with a T cell receptor (TCR)-mediated actin rearrangement, insulin signalling, PI3K/Akt/mTOR pathway, and lipid production. However, the role of Nck1 in regulating glucose metabolism in T cells is still largely unknown. In the present study, the role of Nck1 in glucose metabolism in primary human T cells was investigated. Plasmid encoding Nck1-specific short hairpin RNA (shRNA) was delivered to primary T cells to mediate Nck1 silencing. Plasmids encoding Nck1-specific short hairpin RNA (shRNA) were delivered to primary human T cells to mediate Nck1 silencing. Nck1-knockdown (N1KD) cells were analysed for processes related to glucose metabolism and function. Despite an increased expression of glucose transporter 1 (GLUT1) in N1KD cells, these cells exhibited impaired glucose uptake and ATP production, indicating dysfunction of GLUT1 or altered intracellular glucose metabolism. Nck1 depletion disrupted metabolic signalling characterised by reduced TXNIP and phosphoribosomal protein S6 (pS6) levels, along with an increased phosphorylation of Akt and AMPK. The reduced extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) found in N1KD cells indicated impaired glycolysis and oxidative phosphorylation. Functionally, these metabolic alterations were associated with impaired T cell activation, reduced proliferation, and increased apoptosis. Collectively, Nck1 critically regulated glucose metabolism in T cells, linking metabolic reprogramming to immune function and cell survival.\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 1","pages":"74-86"},"PeriodicalIF":5.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150373","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

IFN-λ: Unleashing Its Potential in Disease Therapies From Acute Inflammation Regulation to Cancer Immunotherapy IFN-λ：释放其在疾病治疗中的潜力，从急性炎症调节到癌症免疫治疗。

IF 5 3区医学

Immunology Pub Date : 2025-05-27 DOI: 10.1111/imm.13954

Benfeng Tang, Zhihong Liu, Huabao Xiong, Junfeng Zhang, Jun Dai

{"title":"IFN-λ: Unleashing Its Potential in Disease Therapies From Acute Inflammation Regulation to Cancer Immunotherapy","authors":"Benfeng Tang, Zhihong Liu, Huabao Xiong, Junfeng Zhang, Jun Dai","doi":"10.1111/imm.13954","DOIUrl":"10.1111/imm.13954","url":null,"abstract":"Type III interferons (IFN-λ), which include IFN-λ1 (or interleukin [IL]-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and IFN-λ4, exert their effects through a unique receptor complex composed of interferon lambda receptor 1 (IFNLR1) and IL-10 receptor subunit beta (IL-10R2). Studies have highlighted their critical role in modulating immune response, particularly in the context of autoimmune diseases, viral infections and cancer. Unlike type I IFNs, which are broadly expressed, IFN-λ displays a more tissue-specific expression pattern, predominantly acting on epithelial cells and certain immune cell types, such as neutrophils and B cells. This specificity allows IFN-λ to play a pivotal role in mucosal immunity, particularly at barrier sites, such as the respiratory and gastrointestinal tracts. Emerging evidence suggests that IFN-λ has a dual role in both enhancing antiviral immunity and regulating inflammation, thus offering a promising therapeutic strategy for diseases like systemic lupus erythematosus, rheumatoid arthritis, asthma and various cancers. However, the precise mechanisms by which IFN-λ influence immune modulation and disease progression remain an area of active investigation. This review aims to provide an overview of the structure, function and signalling pathways of IFN-λ, exploring their role in immune-related diseases and discussing potential avenues for therapeutic intervention.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 2","pages":"197-214"},"PeriodicalIF":5.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13954","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Roles of T Cells in the Development of Metabolic Dysfunction-Associated Steatohepatitis T细胞在代谢功能障碍相关脂肪性肝炎发展中的作用。

IF 5 3区医学

Immunology Pub Date : 2025-05-25 DOI: 10.1111/imm.13943

Zhifa Ge, Qingwei Wu, Chengyu Lv, Qifeng He

引用次数: 0

Endogenous Hydrogen Sulphide Promotes the Ex Vivo Expansion of Haematopoietic Stem Cells by Regulating the Activation of the JAK2/STAT3 Pathway 内源性硫化氢通过调控JAK2/STAT3通路的激活促进造血干细胞的体外扩增。

IF 4.9 3区医学

Immunology Pub Date : 2025-05-22 DOI: 10.1111/imm.13935

Zhiyuan Qiu, Hui Liu, Rongxuan Cao, Shan Wang, Junjun Wang, Wenjun Xu, Rui Zhang, Baohong Wang, Xiaoting Zhang, Qianpeng Li

{"title":"Endogenous Hydrogen Sulphide Promotes the Ex Vivo Expansion of Haematopoietic Stem Cells by Regulating the Activation of the JAK2/STAT3 Pathway","authors":"Zhiyuan Qiu, Hui Liu, Rongxuan Cao, Shan Wang, Junjun Wang, Wenjun Xu, Rui Zhang, Baohong Wang, Xiaoting Zhang, Qianpeng Li","doi":"10.1111/imm.13935","DOIUrl":"10.1111/imm.13935","url":null,"abstract":"<div>\u0000 \u0000 Haematopoietic stem cell transplantation (HSCT) is one of the key strategies for treating various haematologic malignancies. Although there are haematopoietic stem cells (HSCs) in umbilical cord blood (UCB), the number is limited. Thus, the purpose of this work was to investigate if endogenous hydrogen sulphide (H2S) could encourage the ex vivo expansion of HSCs produced from UCB (UCB-HSCs). The CD34+ and CD34+CD38− cells were enriched and separated by immunomagnetic beads. UCB-HSCs were treated with overexpression plasmids of β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulphurtransferase (MPST) and/or stimulated with AG490 (JAK2/STAT3 inhibitor) for 4, 7 or 10 days, respectively. The content of H2S in cells was detected using its assay kit. The proportion and quantity of CD34+, CD34+CD38− and CXCR4+CD34+ cells as well as the ALDH1A1+CD34+ cells in CD34+ cells were detected by flow cytometry. qPCR was used to detect the expression of CD34, CXCR4 and ALDH1A1 in CD34+ cells. Western blot was used to detect the activation of the JAK2/STAT3 pathway in CD34+ cells. The results showed that endogenous H2S enhanced the ex vivo expansion of CD34+ and CD34+CD38− cells, upregulated the expression of CXCR4 and ALDH1A1 during ex vivo expansion of HSCs, and promoted the JAK2/STAT3 pathway in CD34+ cells. However, the aforementioned effects of endogenous H2S were partially reversed by AG490. In conclusion, endogenous H2S promotes the activation of the JAK2/STAT3 pathway to facilitate the ex vivo expansion of UCB-HSCs.\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 4","pages":"534-543"},"PeriodicalIF":4.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127529","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

Inhibition of IRE1α Alleviates Renal Fibrosis and Downregulates M1 Macrophage Activation via the p38 MAPK Pathway 通过p38 MAPK途径抑制IRE1α减轻肾纤维化并下调M1巨噬细胞活化

IF 5 3区医学

Immunology Pub Date : 2025-05-22 DOI: 10.1111/imm.13949

Zichan Guo, Yuting Shen, Xiaxia Yu, Yun Song, Jiyang Zheng, Yuen Zeng, Yazhen Wang, Zhaoyue Fu, Yongli Hou, Dingwen Shi, Liangjian Han, Juan Li, Lihua Chen

{"title":"Inhibition of IRE1α Alleviates Renal Fibrosis and Downregulates M1 Macrophage Activation via the p38 MAPK Pathway","authors":"Zichan Guo, Yuting Shen, Xiaxia Yu, Yun Song, Jiyang Zheng, Yuen Zeng, Yazhen Wang, Zhaoyue Fu, Yongli Hou, Dingwen Shi, Liangjian Han, Juan Li, Lihua Chen","doi":"10.1111/imm.13949","DOIUrl":"10.1111/imm.13949","url":null,"abstract":"<div>\u0000 \u0000 The enhanced M1 macrophage activation and proportion significantly promote the progression of renal fibrosis in the unilateral ureteral obstruction (UUO) model, while the underlying mechanisms need to be further studied. Here, we examined whether or not endoplasmic reticulum (ER) stress contributed to M1 macrophage activation and the mechanisms in this process. In the UUO mouse model, the proportion of M1 macrophages could be significantly increased in the early renal fibrosis, with the ER stress activated. The inhibitor of ER stress (4-PBA) significantly suppressed the activation of M1 macrophages and alleviated the renal fibrosis in the UUO mouse model. Furthermore, the renal fibrosis could be relieved after the administration of IRE1α inhibitor (4μ8C), with the downregulation of ER stress and M1 macrophage activation. Mechanistically, ER stress-enhanced activation of M1 macrophages was regulated through the IRE1α/XBP1s–p38 MAPK pathway. IRE1α-deficient macrophages could alleviate the renal fibrosis in the UUO mouse model. Thus, our findings suggest that the ER stress pathway regulates M1 macrophage activation in the UUO model, which provides a novel therapeutic approach for renal fibrosis.\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 1","pages":"59-73"},"PeriodicalIF":5.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127531","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 Landscape of SPP1 + Macrophages Across Tissues and Diseases: A Comprehensive Review SPP1+巨噬细胞在组织和疾病中的作用：综述

IF 5 3区医学

Immunology Pub Date : 2025-05-21 DOI: 10.1111/imm.13952

Alessandro Palma

{"title":"The Landscape of SPP1\u0000 + Macrophages Across Tissues and Diseases: A Comprehensive Review","authors":"Alessandro Palma","doi":"10.1111/imm.13952","DOIUrl":"10.1111/imm.13952","url":null,"abstract":"Macrophages play a critical role in shaping the immune landscape of various diseases, with secreted phosphoprotein 1 (SPP1)-expressing macrophages emerging as a distinct subset implicated in both cancerous and non-cancerous conditions. Leveraging recent advances in single-cell RNA sequencing, numerous studies have identified SPP1+ macrophages across diverse pathological contexts, shedding light on their functional heterogeneity. In cancer, SPP1+ tumour-associated macrophages contribute to tumour growth, angiogenesis, and immune evasion, often interacting with T cells and stromal components to sustain an immunosuppressive microenvironment. Conversely, in non-cancerous diseases, these macrophages exhibit both profibrotic and disease-promoting properties, depending on the tissue context. This review provides a comprehensive synthesis of the latest findings on SPP1+ macrophages, highlighting their roles in tumour progression, immune suppression, tissue remodelling, and fibrosis. By comparing their shared traits and tissue-specific differences, we explore how SPP1+ macrophages adapt to distinct microenvironments and influence disease progression. Understanding their conserved and context-dependent functions may open new avenues for therapeutic targeting.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 2","pages":"179-196"},"PeriodicalIF":5.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13952","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110589","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

Application and Perspectives of Immunotherapy in Head and Neck Squamous Cell Carcinoma 免疫治疗在头颈部鳞状细胞癌中的应用及展望。

IF 5 3区医学

Immunology Pub Date : 2025-05-21 DOI: 10.1111/imm.13951

Zihao Zhang, Xiaohui Meng, Liang Han

{"title":"Application and Perspectives of Immunotherapy in Head and Neck Squamous Cell Carcinoma","authors":"Zihao Zhang, Xiaohui Meng, Liang Han","doi":"10.1111/imm.13951","DOIUrl":"10.1111/imm.13951","url":null,"abstract":"Head and neck squamous cell carcinoma poses grave challenges to clinicians and patients due to its tumour invasiveness and treatment uncertainties. Despite the substantial improvements in conventional treatment modalities such as surgery, chemotherapy and radiotherapy, the recurrence rate and mortality rate of HNSCC remain stubbornly high. Traditionally, the front-line therapy for recurrent/metastatic HNSCC has been the amalgamation of platinum-based drugs/paclitaxel, 5-fluorouracil and cetuximab, yet it only improves the prognosis of some patients, and the overall treatment situation remains severe. Immunotherapy, as an emerging luminary in the domain of cancer treatment, is committed to improving the tumour microenvironment and stimulating the immune system to perform anti-tumour functions. The continuous updates of immune checkpoint inhibitors have also obtained favourable clinical feedback and are expected to overcome the constraints of traditional therapies. This article elaborates on the trends of immunotherapy within the TME and the progress of immunotherapy, aiming to provide new ideas for treatment regimens in the new therapeutic landscape of HNSCC and offer new hope for patients.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 2","pages":"164-178"},"PeriodicalIF":5.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13951","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110584","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