{"title":"Appetite for destruction: dietary lipids tune the ferroptotic threshold of adaptive immunity","authors":"Pooranee K Morgan, Andrew J Murphy","doi":"10.1111/imcb.70119","DOIUrl":"10.1111/imcb.70119","url":null,"abstract":"<p>Dietary lipids tune the ferroptosis checkpoint in T cells. PUFA-rich diets promote incorporation of oxidizable PUFAs into T-cell membranes, increasing lipid peroxidation and ferroptosis sensitivity. In contrast, MUFA-rich diets favor incorporation of monounsaturated fatty acids that reduce lipid peroxidation and confer ferroptosis resistance. This lipid-dependent balance establishes a ferroptosis checkpoint that regulates T-cell survival and shapes adaptive immune responses, including vaccine efficacy, anti-tumor immunity, CAR-T-cell therapy and immune homeostasis. Created in BioRender. Morgan, P. (2026) https://BioRender.com/k2i6z6b.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"552-555"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758321","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}
Sebastian Cruz-Gomez, Hui Jing Lim, Brunda Nijagal, Yuting Yang, Nicole Lau, Jeffrey YW Mak, David P Fairlie, Hayley Newton, Mariolina Salio, Jose A Villadangos, Hamish EG McWilliam
{"title":"Cytosolic delivery of bacterial metabolites by riboflavin transporters promotes MR1 antigen presentation and MAIT cell recognition","authors":"Sebastian Cruz-Gomez, Hui Jing Lim, Brunda Nijagal, Yuting Yang, Nicole Lau, Jeffrey YW Mak, David P Fairlie, Hayley Newton, Mariolina Salio, Jose A Villadangos, Hamish EG McWilliam","doi":"10.1111/imcb.70130","DOIUrl":"10.1111/imcb.70130","url":null,"abstract":"<p>Major histocompatibility complex class I-related protein 1 (MR1) presents microbial Vitamin B-related metabolite antigens (VitBAg) at the cell surface to activate mucosal-associated invariant T (MAIT) cells. Precisely how antigen-presenting cells capture these MR1 ligands is not known. Here, we show that the most effective route for presentation of bacterial VitBAg involves passage through the cytosol. Consistent with structural similarities with riboflavin, we find that VitBAg presentation is inhibited by riboflavin. We further show that riboflavin carriers transport VitBAg into cells and enhance MR1 antigen presentation to MAIT cells. However, elimination of specific riboflavin carriers does not ablate VitBAg presentation, indicating cells possess redundant mechanisms to internalize this family of MR1 ligands. Our findings provide new insights into the intracellular pathway used by VitBAg to bind MR1 molecules and identify potential approaches to boost MR1-mediated MAIT cell responses for therapeutic benefits.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"595-608"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831381","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}
Beatriz Aires-Lopes, Fernando Souza-Fonseca-Guimaraes
{"title":"Highlights of 2025: advancements in natural killer cell biology","authors":"Beatriz Aires-Lopes, Fernando Souza-Fonseca-Guimaraes","doi":"10.1111/imcb.70121","DOIUrl":"10.1111/imcb.70121","url":null,"abstract":"<p>Recent findings uncover new mechanisms governing NK cell activation, inhibition, metabolism, and memory-like responses, alongside a newly described role in systemic immune regulation via adipose tissue.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"556-559"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758414","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":"Mapping T-cell activation one cell at a time","authors":"Jessica G Borger, Megan F Taylor","doi":"10.1111/imcb.70123","DOIUrl":"10.1111/imcb.70123","url":null,"abstract":"<p>The classical three-signal model of naïve T-cell activation, including T-cell receptor engagement, co-stimulation, and cytokine support, has provided a durable conceptual framework for understanding adaptive immunity. Yet, this linear population model underestimates the spatial, temporal, and cooperative complexity governing individual T-cell fate. Exponential technological advances in genomics approaches over the last decade, including single-cell RNA-sequencing, trajectory inference, and multimodal profiling, have enabled the resolution of cellular heterogeneity and developmental hierarchies at the single cell level. A series of studies published in 2025 demonstrate that CD8<sup>+</sup> T-cell activation is not a singular event but an iterative developmental program distributed across anatomical niches and sequential signaling phases. Distinct waves of T-cell priming refine clonal selection, where lymph nodes function as specialized hubs sustaining stem-like progenitors during chronic infection and cancer, while tissue microenvironments provide late-stage reinforcement or restraint, and noncanonical helper networks restore dysfunctional CD8<sup>+</sup> T cells through local interactions. Collectively, these findings position T-cell activation as a dynamic process shaped by spatial and anatomical organization and branched environmental cues. Mapping T-cell activation one cell at a time has started to reveal a distributed network of developmental checkpoints, raising the prospect that future immunotherapies will target activation trajectories rather than simply triggering activation signals.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"569-573"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758436","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}
Isabella Naylor, Adrian Y S Lee, Joanne Reed, Qian Shen
{"title":"Highlights of 2025: the B-side of LEF1","authors":"Isabella Naylor, Adrian Y S Lee, Joanne Reed, Qian Shen","doi":"10.1111/imcb.70129","DOIUrl":"10.1111/imcb.70129","url":null,"abstract":"<p>In this article of the Highlights of 2025 series, we review the latest discovery of LEF1 function in B cell biology. These discoveries provide novel insights into the LEF1 function on B cell maintenance in cancer and autoimmunity, uncovering new opportunities for the development of a more specific B cell targeting approach.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"582-585"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809028","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}
Timothy Patton, Adam G Nelson, Alexandra J Corbett
{"title":"From transcription to biological translation: regulation and recognition of MR1","authors":"Timothy Patton, Adam G Nelson, Alexandra J Corbett","doi":"10.1111/imcb.70125","DOIUrl":"10.1111/imcb.70125","url":null,"abstract":"<p>The axis of MR1 restricted T-cell immunity has been an area of growing interest over the past decade. In this “Highlights of 2025” perspective, we discuss recent advances in our understanding of the transcriptional regulation of <i>MR1</i>, the distribution of MR1 protein across tissues and the elucidation of novel MR1 ligands. The advances of 2025 have unlocked new methodologies and mechanistic insights, aiding future studies that consider MR1 and its contribution to the development of MR1-restricted T-cell responses in the context of infection, cancer and autoimmunity.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"564-568"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758335","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}
Rebecca Palmer, Olivier Lamiable, Kerry L. Hilligan
{"title":"Highlights of 2025: epithelial-immune circuitry in allergic airway inflammation","authors":"Rebecca Palmer, Olivier Lamiable, Kerry L. Hilligan","doi":"10.1111/imcb.70126","DOIUrl":"10.1111/imcb.70126","url":null,"abstract":"<p>In this Highlights article, allergic asthma and rhinitis are reframed as diseases of epithelial-immune dysregulation. Advances from 2025 establish epithelial-immune circuitry as a central organizing principle of allergic airway inflammation—spanning allergen sensing, memory T-cell function and perpetuation of inflammatory niches—and provide a foundation for next-generation, tissue-directed therapies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"586-589"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809013","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":"Bridging Science and Society: Public Engagement as a Catalyst for Infectious Disease Control and Prevention","authors":"Matthias Eberl, María-Teresa Pérez-Gracia","doi":"10.1111/imcb.70139","DOIUrl":"10.1111/imcb.70139","url":null,"abstract":"<p>This Special Feature highlights the essential role of public engagement in building trust, raising awareness and improving understanding in infectious disease research, control and prevention. In fields such as immunology, microbiology and vaccinology, public engagement ensures that scientific advances are both communicated and applied effectively for improved global health. The present collection of articles presents creative and inspiring approaches to achieve this, from gamification tools that make complex concepts accessible to community-led initiatives that strengthen vaccine confidence among marginalized groups. Together, these contributions reinforce that public engagement requires dialogue, co-creation and the inclusion of diverse perspectives in research and policy. To maximize impact, engagement must be embedded as a core element of academic research and teaching, backed by training, recognition and sustained support. By advocating to make public engagement integral to infectious disease research and preparedness, this Special Feature demonstrates how collaboration between scientists and society can build more resilient and responsive health systems.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"635-638"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222187","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}
Anthony J Farchione, HoChan Cheon, David Vremec, Julika Neumann, Gwenny M Verstappen, Melinda Y Hardy, Mai B Margetts, Lauren J Howson, Lee M Henneken, Maureen Forde, Jason A Tye-Din, Susanne Heinzel, Philip D Hodgkin, Vanessa L Bryant
{"title":"Functional immune profiling reveals CD4+ T cell dysregulation in coeliac disease","authors":"Anthony J Farchione, HoChan Cheon, David Vremec, Julika Neumann, Gwenny M Verstappen, Melinda Y Hardy, Mai B Margetts, Lauren J Howson, Lee M Henneken, Maureen Forde, Jason A Tye-Din, Susanne Heinzel, Philip D Hodgkin, Vanessa L Bryant","doi":"10.1111/imcb.70132","DOIUrl":"10.1111/imcb.70132","url":null,"abstract":"<p>T cells integrate signals from antigen and costimulatory receptors to calibrate response magnitude and quality, with genetically encoded programs shaping activation thresholds for immune tolerance and feedback regulation. Coeliac disease (CeD) is an autoimmune disorder with well-defined genetic risk and immune dysregulation triggered by dietary gluten. However, how genetic risk translates into cell-intrinsic functional variation, particularly within the naïve T-cell compartment, remains poorly defined. Here, we developed the <i>T cell momentum assay</i>, a quantitative functional profiling platform combining standardized T-cell activation with defined stimulus withdrawal to measure proliferation, survival and activation dynamics over time. Integrated with the Cyton2 mathematical model, this approach infers cellular fate programs from population-level dynamics, enabling high-resolution analysis of intrinsic T-cell behavior. Applying this assay to naïve T cells from individuals with CeD and healthy donors (HDs), we identified disease-associated abnormalities predominantly in CD4<sup>+</sup> T cells, including hypoproliferation, reduced IL-2 secretion, impaired survival and delayed downregulation of CD69, indicating prolonged activation and impaired feedback regulation. Distinct early alterations in CD8<sup>+</sup> T cells were also observed. These abnormalities were present in both newly diagnosed individuals and those on a gluten-free diet, supporting a cell-intrinsic phenotype not solely attributable to active inflammation and is consistent with altered baseline immune function. Together, our findings reveal previously unrecognized alterations in naïve T-cell programming in CeD, linking inherited immune variation to functional dysregulation beyond antigen-specific responses. More broadly, the momentum assay offers a scalable, model-informed framework to detect subtle early T cell dysregulation and functionally stratify immune variation across autoimmune diseases.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"613-630"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147961580","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":"Highlights of 2025: advances in the immunopathogenesis of celiac disease","authors":"Jennifer M Chen, Mandeep Singh","doi":"10.1111/imcb.70122","DOIUrl":"10.1111/imcb.70122","url":null,"abstract":"<p>In this research highlight, we explore 5 articles published in 2024 that provide new insight into the underlying immune mechanisms of celiac disease pathogenesis.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 6","pages":"560-563"},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758446","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}