Immunology & Cell Biology最新文献

{"title":"A potential role for monoallelic expression in penetrance of autosomal dominant inborn errors of immunity","authors":"Emily SJ Edwards,&nbsp;Menno C van Zelm","doi":"10.1111/imcb.12856","DOIUrl":"10.1111/imcb.12856","url":null,"abstract":"<p>In this article, we discuss a recent study, where autosomal monoallelic expression of genes underlying Inborn Errors of Immunity were investigated. About 2-10% of genes are predominantly transcribed from a single allele leading to autosomal random monoallelic expression (I). If this is skewed in a cell population from an individual with an autosomal dominant inborn error of immunity, this can lead to a mild to no phenotype (incomplete penetrance) if the wildtype allele is favored (II), or to more severe disease presentation if the variant allele is favored (III).\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 4","pages":"333-336"},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased fatty acid production and macrophage-driven inflammation as key drivers of severe respiratory disease","authors":"Emily M Eriksson,&nbsp;Ivo Mueller","doi":"10.1111/imcb.12852","DOIUrl":"https://doi.org/10.1111/imcb.12852","url":null,"abstract":"<p>In this article, we discuss a recent article by Jia <i>et al.</i>, where high <i>OLAH</i> expression was detected in severe and fatal respiratory disease which was associated with a number of processes and responses. These include high abundance of oleic acid, excessive cytokine release, high viral titres and lipid droplets and increased presence of lung-associated innate cells.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 3","pages":"224-227"},"PeriodicalIF":3.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling the response to interleukin-21 to inform natural killer cell immunotherapy","authors":"Indrani Nayak,&nbsp;Rosalba Biondo,&nbsp;William C Stewart,&nbsp;Rebecca J Fulton,&nbsp;Nina Möker,&nbsp;Congcong Zhang,&nbsp;Salim I Khakoo,&nbsp;Jayajit Das","doi":"10.1111/imcb.12848","DOIUrl":"10.1111/imcb.12848","url":null,"abstract":"<p>Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with mathematical modeling using feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy of activated STATs and NF-κB transcription factors between priming and post-priming phases. The use of IL-21 in solution in the priming of NK cell culture resulted in an improved NK cell proliferation, without compromising cytotoxicity potential or interferon gamma secretion against hepatocellular carcinoma cell lines. Our work provides an integrative framework for interrogating NK cell proliferation and activation for cancer immunotherapy.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 2","pages":"192-212"},"PeriodicalIF":3.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12848","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cyclin-dependent kinase inhibitor AT7519 is a human RORγt agonist","authors":"Kaja Karaś,&nbsp;Joanna Pastwińska,&nbsp;Anna Sałkowska,&nbsp;Iwona Karwaciak,&nbsp;Rafał A Bachorz,&nbsp;Marcin Ratajewski","doi":"10.1111/imcb.12851","DOIUrl":"10.1111/imcb.12851","url":null,"abstract":"<p>AT7519, which inhibits multiple cyclin-dependent kinases, has been extensively investigated in various types of cancer cells. Previous studies have demonstrated the ability of this molecule to suppress the expression of the nuclear receptor retinoic acid–related orphan receptor gamma (RORγ) and several genes involved in hepatocellular carcinoma progression. In this study, we identified a distinct agonistic effect of AT7519 on RORγt, an isoform expressed by various immune cells, including T helper 17 lymphocytes. These immune cells play pivotal roles in shaping the tumor microenvironment and promoting the anticancer response of the immune system. After exposure to AT7519 during differentiation, primary human CD4⁺ T cells presented increased expression of <i>IL17A/F</i>, <i>IFNG</i> and <i>GZMB</i> and decreased expression of <i>PDCD1</i> and <i>CTLA4</i>. These findings elucidate a previously unrecognized facet of AT7519 activity and suggest the potential incorporation of this molecule into immune therapies to augment the effectiveness of diverse anticancer strategies involving anti–programmed cell death protein 1 (anti–PD-1) and anti–cytotoxic T-lymphocyte antigen 4 (anti–<i>CTLA4</i>) regimens.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 3","pages":"317-327"},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAM10 modulates the efficacy of T-cell mediated therapy in solid tumors","authors":"Ahmed ME Abdalla,&nbsp;Yu Miao,&nbsp;Ning Meng,&nbsp;Chenxi Ouyang","doi":"10.1111/imcb.12855","DOIUrl":"10.1111/imcb.12855","url":null,"abstract":"<p><i>Immunology &amp; Cell Biology</i> 2025; <b>103</b>: 213; https://doi.org/10.1111/imcb.12855</p><p>Correction to: <i>Immunology &amp; Cell Biology</i> 2024; https://doi.10.1111/imcb.12826</p><p>The name of one of the authors is incorrect. Ning Ming should be Ning Meng. The correct spelling of this author's name appears in the title above.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 2","pages":"213"},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12855","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An X-tra role for NFκB in gene regulation?","authors":"Sara Berent,&nbsp;Rhys S Allan","doi":"10.1111/imcb.12850","DOIUrl":"10.1111/imcb.12850","url":null,"abstract":"<p>In this Research Highlight, we discuss recent research which shows that TCR-mediated activation and NF-κB signalling play an indispensable role in localising Xist RNA and its interactors to the inactive X chromosome (Xi) in T cells (left and middle). Inhibition of NF-κB disrupts this process, impairing the recruitment of silencing factors and jeopardizing the maintenance of X chromosome inactivation (right).\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 3","pages":"220-223"},"PeriodicalIF":3.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining bone marrow ablation and reconstitution in mice","authors":"Penny Hawkins,&nbsp;James Dooley,&nbsp;Jessica Rodda,&nbsp;Colin Gilbert","doi":"10.1111/imcb.12847","DOIUrl":"10.1111/imcb.12847","url":null,"abstract":"<p>This report presents findings from a group of UK-based researchers with expertise in the use of animal models for bone marrow ablation and reconstitution. The primary aim is to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Bone marrow ablation and reconstitution procedures are performed for a number of different purposes and conducted predominantly in mice. These procedures can induce significant suffering, classified as \"severe\", Category E or Category D/E under European, US and Canadian legislation, respectively. Although severity categorization is not mandated in countries such as Australia and New Zealand, legislation still requires that the level of animal suffering must be minimized to the greatest extent possible. This report identifies specific animal welfare issues and proposes practical measures aimed at reducing both animal use and suffering.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 3","pages":"293-306"},"PeriodicalIF":3.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Learnings from ten years away from “home” as a South American immunologist in Ireland","authors":"Natalia Muñoz-Wolf","doi":"10.1111/imcb.12849","DOIUrl":"10.1111/imcb.12849","url":null,"abstract":"<p>Pursuing an international scientific career is a fantastic opportunity for personal and professional growth, but it also poses unique challenges, which can be particularly daunting for researchers coming from resource-limited countries. Drawing from personal experience, this article provides insights into navigating the transition to working abroad in academia and developing a sustainable career while integrating into a new culture. From predeparture preparations to achieving career independence, I discuss practical aspects of crafting tailored applications to contact potential advisers, contemplating visa-related challenges, establishing collaborations and emphasizing the value of finding appropriate mentorship to help you adapt to new cultural and professional environments. The article also underscores the importance of resilience, adaptability and redefining career success as a dynamic, nonlinear process. I present an original perspective on career planning, inspired by maritime voyage planning, to address the complexities of balancing personal and professional life, particularly during transitional periods. This approach, which combines four key stages of planning, namely, appraisal, planning, execution and monitoring, serves as a model for early-career researchers to navigate the unpredictable tides of academic work and personal life abroad with the goal of sustaining progress and well-being. These reflections aim to empower scientists preparing for or adapting to international research environments, fostering resilience and adaptability for long-term success abroad.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 3","pages":"270-274"},"PeriodicalIF":3.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-seeking bacterial missiles","authors":"George Cavic,&nbsp;Aude M Fahrer","doi":"10.1111/imcb.12844","DOIUrl":"10.1111/imcb.12844","url":null,"abstract":"&lt;p&gt;In this exceptionally elegant and far-reaching study, the Arpaia lab at Columbia University engineer a probiotic &lt;i&gt;Escherichia coli&lt;/i&gt; strain to eliminate cancer.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Working in two mouse models of cancer, CT26 colorectal cancer and B16F10 melanoma, Redenti &lt;i&gt;et al&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; start by identifying cancer-specific sequences. From these, they choose peptides containing (linked) MHCI and MHC II epitopes (about 25–30 amino acids long). They find that encoding a series of these in a plasmid, concatenated, but separated by five glycine-serine repeats, provides good expression of the neoantigens by &lt;i&gt;E. coli&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;They then turned to engineering EcN, a strain of &lt;i&gt;E. coli&lt;/i&gt; isolated by Professor Alfred Nissle in 1917 from a young soldier resistant to infectious diarrhea.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Nissle marketed his discovery as a probiotic (Mutaflor®, still commercially available). Thus, Redenti &lt;i&gt;et al&lt;/i&gt;. start with a safe, non-pathogenic &lt;i&gt;E. coli&lt;/i&gt;, already extensively studied and widely used in humans (albeit orally).&lt;/p&gt;&lt;p&gt;Finding that their neoantigen plasmids express better in &lt;i&gt;E. coli&lt;/i&gt; BL21 than in EcN, they set about modifying EcN to resemble BL21. Curing EcN of cryptic plasmids allows increased expression of the neoantigen-encoding plasmid. They then engineer deletions of two proteases: OmpT, which has roles in biofilm formation and the degradation of complement; and Lon which has pleiotropic roles within the bacterial cell, including oxygen-sensing.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Hence, deleting these proteases, not only reduced degradation of the neoantigen peptides, but also attenuates EcN. Although not discussed by the authors, deletion of the Lon protease may impede the survival of EcN in normal tissues more than in the anoxic core of the tumor, further reducing potential off-target effects. Overall, the authors show that their engineered EcN bacteria show an 80-fold increase in expression of the neoantigen peptides compared with the original EcN, and a 1000-fold increased susceptibility to phagocytosis and clearance from the blood.&lt;/p&gt;&lt;p&gt;In another stroke of genius, the authors next insert the gene for Listeriolysin O (LLO), a pore-forming protein which allows &lt;i&gt;Listeria&lt;/i&gt; to escape into the cytosol after phagocytosis. This has two benefits: improved loading of neoantigen epitopes on MHC class I, and skewing towards a T&lt;sub&gt;H&lt;/sub&gt;1 immune response after the sensing of intracytoplasmic bacteria.&lt;/p&gt;&lt;p&gt;The authors then turn to &lt;i&gt;in vivo&lt;/i&gt; experiments to test their neoantigen-expressing, cryptic-plasmid cured, OmpT&lt;sup&gt;−&lt;/sup&gt;, Lon&lt;sup&gt;−&lt;/sup&gt;, LLO&lt;sup&gt;+&lt;/sup&gt; EcN.&lt;/p&gt;&lt;p&gt;In both of the tumor models, EcN injected i.v. could consistently be cultured from tumors (3–4 days after injection), but could not be cultured from any of the other tissues tested, including the tumor-draining lymph node (TdLN). Despite this, i.v. injection of the EcN bacteria in the CT26 model was sho","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 2","pages":"98-100"},"PeriodicalIF":3.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the dynamics of T-cell responses: a combined approach using EdU incorporation and proliferation dye dilution assay","authors":"Hilde Raaphorst,&nbsp;Sinéad Lougheed,&nbsp;Latifa Saou,&nbsp;Nadine D van Kleef,&nbsp;Irma Rensink,&nbsp;Anja ten Brinke,&nbsp;Julian J Freen-van Heeren,&nbsp;Annelies W Turksma","doi":"10.1111/imcb.12845","DOIUrl":"10.1111/imcb.12845","url":null,"abstract":"<p>Understanding antigen-specific T-cell responses is crucial for advancing immunotherapies and vaccine development. This study proposes a novel approach combining two complementary assays: the 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay (tracking proliferation over 0–48 h) and the VPD450 dye dilution assay (tracking proliferation over 4–6 days). Integrating these techniques provides additional insights into T-cell proliferation kinetics. Both assays were independently optimized using anti-CD3 and anti-CD28 polyclonal T cell stimulation. 1 μM VPD450 is suitable for assessing T-cell proliferation. The EdU concentration should match the stimulation strength, requiring higher concentrations to efficiently track DNA replication detection during increased cellular division. Day 5 was the optimal read-out day for the EdU incorporation assay. We then combined the VPD450 dye dilution and EdU incorporation assays. As a proof of principle, we stimulated PBMCs from healthy donors with tetanus toxoid to assess antigen-specific T-cell responses. Additionally, we demonstrated the assay's application in drug research by evaluating proliferation in a mixed lymphocyte reaction with abatacept, an agonistic anti-CTLA-4 antibody. This combined approach offers qualitative insights into T-cell proliferation kinetics, beneficial for assessing novel vaccine efficiency or for designing new treatments targeting T cell proliferation, such as in autoimmune settings.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 2","pages":"178-191"},"PeriodicalIF":3.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}