Immunology最新文献

{"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":"Flagellins as Vaccine Adjuvants and Cancer Immunotherapy: Recent Advances and Future Prospects.","authors":"Asma Talukder, Md Mijanur Rahman, Md Sifat Rahi, Dean L Pountney, Ming Q Wei","doi":"10.1111/imm.70001","DOIUrl":"https://doi.org/10.1111/imm.70001","url":null,"abstract":"<p><p>Flagellin, an essential structural protein of bacterial flagella, has emerged as a potent modulator of both specific and nonspecific immunity, demonstrating significant potential as a vaccine adjuvant and carrier. By inducing the release of pro-inflammatory cytokines like IL-1β, TNF-α, IL-6, IL-8, and IL-12, flagellin activates the innate immune system, enhancing antigen-specific adaptive immune responses mediated by tumour-specific type 1 helper T cells and cytotoxic T cells, thus positioning it as a valuable adjuvant or complementary therapy for various cancers and infectious diseases. This review explores recent strategies, innovations, and clinical applications of flagellin-based immunotherapies, particularly in the context of infectious diseases and cancers. Flagellin from Salmonella typhimurium has been extensively studied as a vaccine adjuvant for diseases like HIV, influenza, dengue, West Nile virus, poultry cholera, and bursal diseases and shows promise in treating lung metastasis, melanoma, colon, and prostate cancers. It has also proven effective against multidrug-resistant bacteria, including Pseudomonas aeruginosa and S. typhimurium. Notably, S. typhimurium flagellin-based vaccines for influenza have progressed to clinical trials. Additionally, flagellins from S. typhi, S. enteritidis, P. aeruginosa, and Escherichia coli are being evaluated as vaccine candidates for plague, malaria, and infections caused by P. aeruginosa and E. coli. In cancer therapy, flagellin-based treatments, especially when combined with tumour antigens, have exhibited the ability to enhance anti-tumour immunity and improve patient outcomes. Other flagellin-based vaccines derived from S. Dublin, S. munchen, and Vibrio vulnificus have been employed in the treatment of prostate, lung, liver, breast, cervical, and colorectal cancers, as well as lymphoma, melanoma, and radiation-induced mucositis. Mobilan, a recombinant non-replicating adenovirus vector expressing Salmonella flagellin, is currently in a phase Ib clinical trial for prostate cancer. Overall, bacterial flagellin treatments are generally safe, well-tolerated, and associated with minimal side effects, making them a promising option for managing infectious diseases and cancers.</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":"144257930","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}

{"title":"Inflammation Perfect Storm: Cancer, Climate and Polarisation.","authors":"Claudio Vieira da Silva","doi":"10.1111/imm.70000","DOIUrl":"https://doi.org/10.1111/imm.70000","url":null,"abstract":"<p><p>Chronic systemic inflammation is increasingly recognised as a central pathological state driving the global burden of non-communicable diseases, most notably cancer, and significantly exacerbated by environmental stressors linked to climate change. This review elucidates the intricate and synergistic relationship between chronic inflammation and cancer, further amplified by the compounding effects of climate change and contemporary sociopolitical polarisation. We examine how biological, environmental and psychosocial factors converge to worsen chronic inflammation and increase cancer risk. Addressing this \"perfect storm\" of converging health threats necessitates a holistic and integrated approach that considers biological vulnerabilities, environmental degradation, the socioeconomic burden of health inequities, and the profound societal impacts of political polarisation to effectively mitigate this escalating global health crisis and promote health equity.</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":"144266083","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}