Immunology最新文献

{"title":"CD73 Expression by CD4⁺ T Cells Marks Early Effector Memory T Cells.","authors":"Luxia Chen, Sabine Ring, Anna Jurga, Florian C Kurschus, Alexander Enk, Karsten Mahnke","doi":"10.1111/imm.70011","DOIUrl":"https://doi.org/10.1111/imm.70011","url":null,"abstract":"<p><p>CD73 is a membrane bound ectoenzyme, dephosphorylating adenosine mono- and di-phosphate to immunosuppressive adenosine. It is strongly expressed by CD4⁺CD25⁺Foxp3⁺ regulatory T cells, but when analysing conventional CD4⁺ T cells only 50% express CD73. When analysing these two clearly distinct (i.e., CD73⁺ and CD73^-) populations, we found that the naïve CD73⁺CD4⁺ subset exerted superior proliferation over the CD73^-CD4⁺ cells, was more resistant to activation induced cells death (AICD) and was prone to develop into a \"Th1-like\" cell type, expressing the prototypic cytokines (IFN-γ, TNF-α) and specific transcription factors (i.e., Tbx21). Upon transfer into lymphopenic hosts, CD73⁺CD4⁺ cells exhibited increased proliferation and survival, and accumulated in inflammatory tissues, developing a CD44⁺CD62L^- effector memory phenotype. Therefore, we conclude that CD73 in naïve CD4⁺ T cells functions as a promotor of survival and proliferation of T cells, as well as a marker for their further differentiation into effector T cells.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505578","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}

{"title":"Radiofrequency Ablation and Immunotherapy: Orchestrating the Immune Microenvironment for Improved Hepatocellular Carcinoma Control.","authors":"Liu Yang, Shuhang Wei, Zongxin Liu, Qiqi Liu, Zhen Yu, Yuemin Feng, Qiang Zhu","doi":"10.1111/imm.70004","DOIUrl":"https://doi.org/10.1111/imm.70004","url":null,"abstract":"<p><p>Radiofrequency ablation (RFA) is a radical treatment modality for early-stage hepatocellular carcinoma (HCC). In addition to directly eliminating tumour cells, RFA induces changes in infiltrating cells within the liver tumour immune microenvironment (TIME), thereby eliciting anti-tumour immune effects. Moreover, incomplete radiofrequency ablation (IRFA) induces an immunosuppressive tumour microenvironment, which inhibits anti-tumour immune responses and promotes tumour recurrence and metastasis. Immunotherapy, a systemic treatment, activates or enhances the immune system to recognise and eliminate tumour cells. Thus, orchestrating the TIME makes it possible to combine RFA and immunotherapy, which may significantly enhance the anti-tumour immune response to target residual tumour cells. This combinatorial approach may emerge as a pivotal strategy to augment HCC control and mitigate post-RFA recurrence. This review discusses how RFA modulates the TIME in HCC, and the immune-related mechanisms leading to tumour cell survival and invasion after IRFA. Finally, we summarise the combined mechanisms of the two modalities on TIME, and their clinical implications for treating HCC, aiming to provide new insights for the combined strategy of RFA and immunotherapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505579","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}

{"title":"γδT Cells in IBD: Beneficial or Detrimental?","authors":"Baoqing Xu, Jianbin Ji, Lingling Ma, Chunyan Wang, Lianjing Pang, QingChao Song, Yang Liu, Zhenghua Zhou, Fanfan Qu","doi":"10.1111/imm.70012","DOIUrl":"https://doi.org/10.1111/imm.70012","url":null,"abstract":"<p><p>γδT cells play a crucial role in inflammatory bowel disease (IBD). Studies have shown that the number, subsets and secreted cytokines of γδT cells undergo changes in IBD. However, whether γδT cells are beneficial or detrimental in IBD remains controversial. Some studies suggest that γδT cells have a protective role in colitis, while others indicate that the expansion and activation of γδT cells may exacerbate colitis. Several studies have explored γδT cell-based therapies for immune disorders, and γδT cell-based therapy for IBD has emerged as a promising research direction. There are numerous reviews of γδT cells and autoimmune diseases, but few reviews focus on γδT and IBD. Therefore, this article briefly summarises the current understanding of γδT cells in IBD.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496108","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}

{"title":"Palmitoylethanolamide (PEA) Induces an Increase in Spleen Regulatory T Cells, Reduces CD8⁺ Cells and TNF-α Levels in Target Organs, and Protects Mice From Graft-Versus-Host Disease-Related Mortality Through PPAR Activation Without Compromising the Graft-Versus-Tumour Response.","authors":"Bárbara Betônico Berg, Zara Desiree Tonidandel Campos, Gioconda Muniz Fiorenza Ruggio, Ana Flávia Santos Linhares, Bárbara Maximino Rezende, Stêfany Bruno de Assis Cau, Thiago Roberto Lima Romero, Mauro Martins Teixeira, Vanessa Pinho, Marina Gomes Miranda Castor","doi":"10.1111/imm.70010","DOIUrl":"https://doi.org/10.1111/imm.70010","url":null,"abstract":"<p><p>Graft-versus-host disease (GVHD), a secondary complication of bone marrow transplantation, leads to the development of a systemic inflammatory illness in the host, resulting in high mortality and morbidity. Current therapies lack prophylactic effectiveness and often fail to achieve an optimal immunological balance between inflammation and immunosuppression. In this study, we investigated the effects of palmitoylethanolamide (PEA), an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory, and neuroprotective effects, on the complex pathology of GVHD. Treatment with PEA reduced clinical disease severity in GVHD mice, leading to an 80% increase in survival rates. Additionally, PEA created an immunoregulatory environment in the spleen by reducing the activation of CD3⁺CD4⁺ cells. In the intestine, PEA protected against damage, reduced the number of CD3⁺CD4⁺ and CD3⁺CD8⁺ cells, and suppressed the activation of CD3⁺CD8⁺ cells. PEA also decreased the levels of TNF-α in the intestine and increased IL-10 production. Furthermore, in the liver, PEA treatment reduced the number of CD8⁺ cells, the activation of CD3⁺CD4⁺ and CD3⁺CD8⁺ cells, and TNF-α levels. The effect of PEA on survival was dependent on Peroxisome Proliferator-activated receptor gamma (PPAR-γ) activation but did not rely on cannabinoid (CB) receptors activation. In addition to GVHD protection, PEA treatment did not interfere in the graft-versus-tumour response. These results demonstrate the therapeutic potential of PEA as a promising option for the treatment of GVHD, balancing inflammation and immunosuppression, and improving both survival and clinical outcomes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496107","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}

{"title":"Acute Plasmodium yoelii 17XNL Infection During BCG Vaccination Limits T Cell Responses and Mycobacterial Growth Inhibition.","authors":"Emily Tangie, Nawamin Pinpathomrat, Rachel Tanner, Nai-Jen Hsu, Alexandra J Spencer, Muazzam Jacobs, Helen Mcshane, Roanne Keeton","doi":"10.1111/imm.70006","DOIUrl":"10.1111/imm.70006","url":null,"abstract":"<p><p>Tuberculosis and malaria overlap in many sub-Saharan African countries where Bacillus Calmette Guérin (BCG) vaccination is routinely administered. The aim of this study was to determine whether the timing of BCG vaccination in relation to a malaria infection has implications for BCG vaccine efficacy. Mice were intradermally vaccinated with BCG either 4 weeks before infection with blood-stage Plasmodium yoelii 17XNL, at 13 days post-infection (during an acute blood-stage malaria infection) or 21 days post-infection (after clearance of P. yoelii 17XNL infection). Ex vivo control of mycobacterial growth by splenocytes was used as a surrogate of protective efficacy, and PPD-specific T-cell responses were quantified by flow cytometry. No differences in mycobacterial growth control were detected between BCG vaccinated mice and groups receiving vaccination prior to or after clearance of P. yoelii 17XNL infection. Poorer control of mycobacterial growth was observed following BCG vaccination administered during an acute malarial infection compared to BCG vaccination only or BCG vaccination after blood-stage malaria infection, and mycobacterial growth negatively correlated with the magnitude of total cytokine production from PPD-specific CD4⁺ T cells (p < 0.0001). Delayed BCG vaccination beyond the neonatal period may increase the risk of concurrent malarial infections with the potential to reduce BCG efficacy in children in malaria-endemic areas.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333038","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}

{"title":"CD59, Disulphide-Locked Human C9 and Horse C9 Inhibit Human Membrane Attack Complex Assembly by Similar Mechanisms.","authors":"Rebekah S Cooke, Bradley A Spicer, Richard A Harrison, Michelle A Dunstone, B Paul Morgan, Wioleta M Zelek","doi":"10.1111/imm.70008","DOIUrl":"https://doi.org/10.1111/imm.70008","url":null,"abstract":"<p><p>Five plasma proteins, C5b, C6, C7, C8 and C9, assemble in a step-wise manner to form the membrane attack complex (MAC) which inserts into target cell membranes to cause lysis. The membrane regulator CD59 binds nascent C5b-8, preventing C9 recruitment and polymerisation into the lytic pore. A disulphide-locked C9 ('C9lock'; C9_F262C/V405C) lacked haemolytic activity in standard assays because the unfolding required for pore formation was prevented, while horse C9 (HoC9) lacked haemolytic activity suggested to be a consequence of species incompatibility in MAC assembly. In this study, we compared the impact of soluble CD59 (sCD59), C9lock and HoC9 on MAC assembly. C9lock and sCD59 were generated recombinantly, while HoC9 and human C9 (HuC9) were affinity-purified from serum. Binding and haemolytic assays were used to identify and compare the modes of action of MAC binding and inhibition by sCD59, C9lock and HoC9. We show that sCD59, C9lock and HoC9 all inhibited human serum mediated haemolysis in both classical and alternative pathways. In reactive lysis assays, all three inhibitors bound immobilised C5b-8 but not C5b-7 intermediates on ELISA wells and gpE, and competitively blocked C9-mediated lysis of gpE. Each of the inhibitors also bound mouse and rat C5b-8 sites on gpE and blocked human C9-mediated lysis. This work clarifies the functional differences between HoC9 and human C9 and highlights the mechanistic similarities of the diverse MAC inhibitors (C9lock, sCD59 and HoC9). These agents not only provide useful tools for analysis of MAC assembly but also signpost novel strategies for specific MAC inhibition in conditions where MAC formation contributes to pathology.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309911","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}

{"title":"Should We Advance Our Understanding of Immunoglobulin E in Viral Immunity?","authors":"Amanda Izeli Portilho, Valéria Oliveira Silva, Luis Fernando de Macedo Brigido, Elizabeth De Gaspari","doi":"10.1111/imm.70007","DOIUrl":"https://doi.org/10.1111/imm.70007","url":null,"abstract":"<p><p>Immunoglobulin E has been extensively studied in allergies and parasitic diseases. However, antigen-specific IgE has been identified as part of the humoral response to some viruses, including Respiratory syncytial virus (RSV), Human rhinovirus (HRV), Influenza, Hepatitis B virus (HBV), Human immunodeficiency virus (HIV), Herpes simplex virus (HSV), Dengue virus (DENV) and SARS-CoV-2. In this brief article, we have reviewed key aspects of IgE function and structure, and summarised the findings about this antibody in virus-specific immune response. To date, IgE effector mechanisms in the face of viruses have been almost unexplored through functional assays. We speculate on possible functionalities, such as neutralisation, cytotoxicity and immunopathology of viral diseases, and provide insights about gaps to fill in future research.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293690","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}

{"title":"PD-1 Regulates the Glycolytic Pathway to Reverse Abnormal CD4⁺ T Cell Differentiation and Alleviate Hashimoto's Thyroiditis.","authors":"Xiao Jiang, Tao Luo, Xinyu Zhao, Pengqian Li, Xiaotong Gu, Chuchu Wan, Xingjie Xie, Haixia Liu","doi":"10.1111/imm.13953","DOIUrl":"https://doi.org/10.1111/imm.13953","url":null,"abstract":"<p><p>Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease lacking a specific cure. This study endeavours to explore the role of PD-1 in modulating glycolysis during CD4⁺ T cell differentiation in HT. The lactate and glucose content in different groups was assessed using lactate and glucose assay kits. The tissue and cellular expression of HK2 and LDHA proteins was examined through Western blot analysis, while Glut1 expression and the ratio of Treg/Th17 cells were analysed using flow cytometry. The glycolysis levels in the HT group were higher than those in the control group. Additionally, the HTE group exhibited a decreased proportion of CD4⁺ CD25⁺ Tregs and an increased proportion of CD4⁺ TH17 cells compared to the healthy control group. Following the addition of PD-1 inhibitors to the activated group, both the glycolysis levels and CD4⁺ T cell differentiation showed improvement. PD-1 can regulate aberrant CD4⁺ T cell differentiation by modulating the glycolytic pathway.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274772","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}

{"title":"A Novel Small Molecule ITK Inhibitor Suppresses Th2/Th17 Differentiation and Attenuates Airway Inflammation in a Mouse Model of HDM-Induced Asthma.","authors":"Zhaoxi Guo, Fuqiang Ye, Yongyou Zhang, Dong Xu, Xuesong Shi, Chen Wang, Juanjuan Zhu","doi":"10.1111/imm.70003","DOIUrl":"https://doi.org/10.1111/imm.70003","url":null,"abstract":"<p><p>Interleukin (IL)-2-inducible T cell kinase (ITK) is essential for T cell receptor (TCR) signalling and plays a pivotal role in asthma pathogenesis. Thus, ITK inhibitors have therapeutic potential in T cell-derived allergic airway inflammation. Nevertheless, no ITK inhibitors are currently approved for asthma treatment, warranting the need to excavate potent small-molecule ITK inhibitors. Here, a novel small-molecule ITK inhibitor C-161 was discovered by compound screening. In silico docking and surface plasmon resonance (SPR) confirmed that C-161 directly binds to the ITK kinase domain. In vitro cellular assays demonstrated that C-161 prevents TCR-induced proinflammatory cytokine release as well as activation and differentiation of Th2 and Th17 cells in a dose-dependent manner. In vivo assays demonstrated that C-161 administration ameliorates the progression of asthma by mitigating infiltration of inflammatory cells and decreasing mucus and IgE production. Additionally, C-161 markedly suppressed airway inflammation by inhibiting Th2/Th17-related immune responses with declined IL4, IL5, IL13 and IL17A expression. Collectively, our study uncovers a novel ITK-specific small molecule inhibitor, C-161, as an attractive lead compound for developing drugs to treat asthma.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283810","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}

{"title":"IL16 Promotes Plasma Cell Differentiation.","authors":"Ying Gao, Jie Li, Fangxia Li, Ran Jia, Shuai Liu, Mingyu Wang, Na Tian, Wendi Wei, Linlin Kuang, Ruiliang Zhu, Xiaozhen Liang","doi":"10.1111/imm.70002","DOIUrl":"https://doi.org/10.1111/imm.70002","url":null,"abstract":"<p><p>The regulation of terminal differentiation of B cells into plasma cells is influenced by transcription factors, epigenetics, and cytokines. Both human and murine B cells possess the capacity to produce interleukin 16 (IL16), a pleiotropic cytokine that serves as a chemoattractant. Despite its production, the precise role of IL16 in B cells has remained elusive. In this study, we showed that IL16 overexpression promoted primary B cell differentiation into B220^lowCD138⁺ plasma cells. This effect was independent of the secreted form of IL16. The overexpression of IL16 resulted in an increase in the expression of plasma transcription factors Blimp-1, IRF4, and Xbp-1, as well as the expression of immunoglobulin genes. Consistently, upon the inoculation of mice with influenza A virus, the absence of IL16 led to a decrease in the number of plasma cells and the production of virus-specific antibodies. Our data demonstrate that IL16 contributes to the terminal differentiation of B cells to plasma cells.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266082","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}