ImmunoHorizons最新文献

{"title":"PDLIM2 repression: a common mechanism in viral lung infection.","authors":"Feng Gao, Yongzheng W Chen, Steven D Shapiro, Gutian Xiao, Zhaoxia Qu","doi":"10.1093/immhor/vlag010","DOIUrl":"10.1093/immhor/vlag010","url":null,"abstract":"<p><p>PDLIM2, a PDZ-LIM domain-containing protein expressed highest in the lung and immune cells, serves as a unique tumor suppressor and immune modulator, mainly by turning off the activation of the master transcription factors NF-κB and STAT3. While its role in cancer is established, the involvement of PDLIM2 in viral infection remains unclear. Here we analyzed public gene expression data of blood leukocytes, bronchoalveolar lavage cells, and lung tissues from uninfected healthy humans and those infected with the respiratory virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza. We found that PDLIM2 expression was repressed by viral infection, and notably, this repression correlated with the severity of infectious diseases. Consistently, the expression level of PDLIM2 was negatively associated with NF-κB and STAT3 activity across a diverse range of cell types, such as macrophages, monocytes, neutrophils, T cells, alveolar type 1 and 2 epithelial cells, airway epithelial cells, and fibroblasts. Accordingly, cells with low PDLIM2 expression exhibited aberrant activation of signaling pathways essential for cellular functions and immune responses. These findings highlight PDLIM2 repression as a common mechanism underlying human viral infectious diseases and suggest PDLIM2 as a potential biomarker and therapeutic target for disease prognosis, prevention, and treatment.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health.","authors":"Oliver Richards, Megan Cotterell, Catherine A Thornton, April Rees","doi":"10.1093/immhor/vlag013","DOIUrl":"10.1093/immhor/vlag013","url":null,"abstract":"<p><p>Reproductive disorders such as endometriosis and polycystic ovary syndrome (PCOS) are increasingly recognized as immune-mediated conditions, yet their immunopathology remains poorly understood. Menstrual blood, a noninvasive and biologically relevant sample, offers a unique window into reproductive tract immunity but has been underutilized in this context. We optimized Cytek's® 25-color high-dimensional flow cytometry panel by incorporating a mitochondrial dye to investigate immune cell profiles in menstrual mononuclear cells (MMCs) from healthy individuals, and those with endometriosis or PCOS, in comparison with matched peripheral blood mononuclear cells (PBMCs). This enabled detailed assessment of 40 immune cell subsets and 546 immunological parameters, including markers of activation, exhaustion, migration, and mitochondrial content. MMCs displayed a distinct immune landscape compared to PBMCs, enriched with tissue-resident NK cells, macrophages, and dendritic cells, alongside changes in mitochondrial mass for various cell subsets and other markers such as PD-1. These findings support a metabolically active, tissue-adapted immune environment within menstrual fluid, representative of the reproductive tract. Exploratory analyses of MMCs from individuals with endometriosis or PCOS revealed disease-specific trends: for example, mitochondrial mass differed across Tregs, CD4 central memory cells, plasmablasts, and cDC1s, with endometriosis and PCOS exhibiting distinct patterns rather than a uniform \"reproductive disorder\" phenotype. Although these disease-associated findings did not consistently reach statistical significance due to the small cohort size, they demonstrate the potential of menstrual blood immunoprofiling to uncover biologically meaningful differences across diverse immune cell populations. Together, this study establishes menstrual fluid as a valuable, non-invasive sample for immunological assessment and a promising avenue for future biomarker discovery in reproductive disorders.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory syncytial virus mRNA vaccine-induced immunity and protection against subgroups A and B in mice.","authors":"Sujin Lee, Jack Yoon, Savannah Shooter, David S Pak, Binh Ha, Christina A Rostad, Larry J Anderson, Raymond F Schinazi, Baek Kim","doi":"10.1093/immhor/vlag006","DOIUrl":"10.1093/immhor/vlag006","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) is a major global cause of severe lower respiratory tract infections in infants and older adults. RSV has 2 subgroups, A (RSV-A) and B (RSV-B), which circulate together with different patterns of dominance. A vaccine must protect against both. Reccently, prefusion F protein-based vaccines for maternal and older adult populations achieved ∼70% efficacy, and Moderna's mRNA vaccine for older adults further underscores the potential of mRNA platforms. Here, we report preclinical evaluation of VER-027, a novel mRNA vaccine encoding prefusion F proteins from both RSV-A and RSV-B. A 2-dose intramuscular regimen induced high pre-F-specific immunoglobulin G (IgG) titers, potent neutralizing activity against both subgroups, and robust F85-93-specific CD8+ T cell responses. All mice vaccinated with this mRNA vaccine were fully protected against RSV-A and RSV-B challenge. These findings support VER-027 as a strong candidate for clinical development as a dual-subgroup RSV vaccine.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT6-IP-dependent inhibition of type 2 innate and Th2 adaptive immunity in the murine lung.","authors":"Haya Aldossary, Rami Karkout, Véronique Gaudreault, Lydia Labrie, Jichuan Shan, Elizabeth D Fixman","doi":"10.1093/immhor/vlag012","DOIUrl":"10.1093/immhor/vlag012","url":null,"abstract":"<p><p>Type 2 airway inflammation is one of the main characteristics of allergen-induced asthma. Evidence from animal studies supports a model in which inhalation of allergens triggers epithelial cell release of alarmin cytokines, including IL-33, which activate a number of innate cells in the lung, including group 2 innate lymphoid cells (ILC2s), which produce large amounts of IL-13 and IL-5, to amplify allergic inflammation. Amongst other activities, ILC2-derived IL-13 promotes DC migration to the lung draining mediastinal lymph nodes (MLNs). Our published data indicate that topical administration of an immunomodulatory peptide, STAT6-IP, at the time of antigen priming inhibits T helper 2 adaptive immunity in murine models of asthma, at least in part, through inhibition of dendritic cells (DCs). In this study, we sought to clarify inhibitory activity of STAT6-IP toward DC responses in the lung and the lung draining MLNs induced by IL-33 and ovalbumin (OVA). Our data show that STAT6-IP reduced expansion of total and IL-13-producing ILC2s in OVA/IL-33-treated mice. STAT6-IP also inhibited OVA/IL-33-induced recruitment to and activation of lung DCs, which in turn reduced DC migration and CD4+ Th2 differentiation in the lung MLNs. When challenged several weeks later with OVA, allergic inflammatory responses, including airway hyperresponsiveness, were reduced in STAT6-IP-treated mice. STAT6-IP retained inhibitory activity whether delivered before or after OVA/IL-33 and activity coincided with expansion of IL-13-producing ILC2s. Altogether, our findings provide insight into mechanisms by which STAT6-IP interacts with innate immune cells of the lung to reduce maladaptive type 2 innate and T helper 2 adaptive immunity.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypically similar but functionally distinct NK cell populations within the human maternal-fetal interface.","authors":"Marie Frutoso, Caitlin S DeJong, Raj Shree, Stephen A McCartney, Martin Prlic","doi":"10.1093/immhor/vlag001","DOIUrl":"10.1093/immhor/vlag001","url":null,"abstract":"<p><p>Natural killer (NK) cell function within tissues extends beyond exerting cytotoxicity, encompassing a range of functions that are just starting to become fully elucidated. In the context of human placentation, NK cells play a key role in enabling initial placentation, which is associated with the acquisition of tolerance-like properties. If and to which extent NK cells maintain these tolerance-like properties over the course of human pregnancy is still poorly understood. We asked if NK cells isolated from the decidual-placental interface of full-term human pregnancies are able to exert effector function. We observed a significant and striking lack in the ability of NK cells isolated from the decidual-placental interface (DPI) to produce interferon-g (IFN-γ) in response to the activating cytokines interleukin (IL)-12, IL-15, and IL-18. In contrast, NK cells from the decidua retained their responsiveness to cytokine-mediated activation. Notably, CD103+CD69+ tissue-resident NK cells were present in both DPI and decidua, yet exhibited distinct effector function from one another. Using high-parameter flow cytometry and single-cell sequencing, we found that this functional discrepancy was not directly predictable based on their cell surface phenotype or cell transcript. Together, our findings reveal the presence of distinct functional resident NK cell populations in 2 anatomically adjacent tissues at healthy full-term pregnancies.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine tuning of TCR signaling via CD8αβ and PD-1 and the fate of autoreactive thymocytes during negative selection.","authors":"Martha C Zúñiga, Sangwon Hyun, Jacob Du, Shahar Dubiner, Alicia Freedman-Goretsky, Yitzhar Goretsky, Anita Pothukuchi, Nicholas A Y Fong, Alexander Berg, Caitlin Davis, Megumi Barata, Tyler M Deveau, Alisa Sas, Stefan Abreo, Bryan Kim, An Nguyen, Jordan Schneider, Alanna White","doi":"10.1093/immhor/vlaf078","DOIUrl":"10.1093/immhor/vlaf078","url":null,"abstract":"<p><p>During thymocyte development, positive selection produces cells whose T cell receptors (TCRs) bind to self MHC. Then, negative selection culls most thymocytes whose TCRs have too high an affinity for self MHC+peptide. Signal transduction events control these processes. CD8-αβ (via CD8-β) recruits p56lck to the immunological synapse and promotes signaling through the TCR. Conversely, PD-1 attenuates TCR signal transduction. We examined the roles of CD8-β and PD-1 in the survival of thymocytes in H-2k haplotype mice expressing a transgenic BM3 TCR, which has high affinity for the allogeneic H-2Kb MHC I molecule. In transgenic mice expressing both H-2Kb in the thymic medulla and the BM3 TCR, apoptosis eliminates most (but not all) post-selection thymocytes. To analyze the roles of CD8-β and PD-1 in the survival of post-selection thymocytes, we devised a novel probabilistic gating strategy employing Gaussian mixture models and statistical methods using sliding windows and changepoint detection. We found that at high levels of CD8-β and therefore high levels of CD8-αβ), thymocytes are prone to apoptosis, regardless of the PD-1 level. At intermediate levels of CD8-β, thymocyte survival increases concordantly with increasing PD-1 levels. At low levels of CD8-β, thymocyte survival is high regardless of the PD-1 level. Surviving DPlo post-selection thymocytes give rise to PD-1+CCR7+DN and PD-1+CCR7-DN post-selection thymocytes, which appear to become DN T cells and IELs, respectively. Thus, PD-1 appears to promote the survival of both IEL precursors and thymocytes destined for other fates. More strikingly, downregulation of CD8-β is a hallmark of autoreactive MHC I-restricted thymocytes that survive negative selection.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac macrophages at the crossroads of inflammation, memory, and repair.","authors":"Yiliang Chen","doi":"10.1093/immhor/vlag003","DOIUrl":"10.1093/immhor/vlag003","url":null,"abstract":"","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 SI","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages in human atherosclerotic plaques in the era of single-cell and spatial transcriptomics.","authors":"Adil Ijaz, Adil Rasheed, Marco Orecchioni","doi":"10.1093/immhor/vlaf089","DOIUrl":"10.1093/immhor/vlaf089","url":null,"abstract":"<p><p>Macrophages are central players of inflammation, lipid metabolism, and remodeling in atherosclerotic plaques. Historically simplified into \"M1\" and \"M2\" polarization states, their biology has been fundamentally redefined by single-cell and spatial transcriptomic technologies. Over the past decade, these approaches have identified multiple macrophage subsets within human atheromas, each driven by distinct metabolic and cytokine signatures and occupying discrete spatial niches. Human single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and multimodal omic profiling collectively demonstrate that macrophage subsets extend far beyond fixed polarization states to engage their long-recognized functions in the atheroma, including inflammation, lipid handling and repair. These findings now link macrophage identity to microenvironmental cues, vascular location, and disease stage. Importantly, these data demonstrate that these macrophages do not exist in mutually exclusive states and can transition between these subtypes in response to these aforementioned factors. Here we synthesize these advances, focusing on human data describing macrophage diversity, spatial organization, and metabolic function, and discuss how this knowledge is reshaping mechanistic models of atherosclerosis and the potential therapeutic targeting of macrophage-mediated pathology.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 SI","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trained immunity: new paradigm in the immunological memory of cardiovascular disease.","authors":"Emma Hope, Azuah L Gonzalez, Lola S Norman, Hunter C Smith, Jean W Wassenaar, Kasey C Vickers, Jonathan D Brown, Amanda C Doran","doi":"10.1093/immhor/vlag008","DOIUrl":"10.1093/immhor/vlag008","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) remains the leading cause of death worldwide, despite significant progress in identifying and managing traditional risk factors such as hyperlipidemia, hypertension, and diabetes. While targeted therapies addressing these factors reduce the risk of primary and secondary cardiac events, a substantial \"residual risk\" persists even after successful clinical intervention. This residual risk has prompted renewed interest in understanding the long-term biological effects of cardiovascular risk factors, particularly through the lens of chronic inflammation. Recent advances highlight a pivotal role for trained immunity-a form of innate immune memory driven by epigenetic and metabolic reprogramming-in driving this inflammation. Unlike adaptive immune memory, trained immunity occurs in innate immune cells and enhances their responsiveness to subsequent, unrelated stimuli. Emerging evidence suggests that various cardiovascular risk states, including hypercholesterolemia, obesity, and diabetes, can induce trained immunity, leading to heightened inflammatory tone that persists over time. Cardiac macrophages, as central mediators of tissue homeostasis and inflammation in the heart, are increasingly recognized as critical targets of this phenomenon. In this review, we explore how established cardiovascular risk factors can induce trained immunity on cardiac macrophages and examine the implications for disease progression, myocardial remodeling, and post-injury repair. Finally, we discuss emerging therapeutic strategies aimed at modulating trained immunity to reduce residual cardiovascular risk, offering a new frontier in the prevention and treatment of CVD.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 SI","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage efferocytosis in cardiovascular disease: mechanisms and therapeutic implications.","authors":"Neha Gupta, Yu Liu, Bishuang Cai","doi":"10.1093/immhor/vlag002","DOIUrl":"10.1093/immhor/vlag002","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) account for millions of deaths worldwide each year, underlining their significant impact on global health. An expanding body of evidence identifies atherosclerosis, myocardial infarction, heart failure, and ischemic stroke as major contributors to this burden. Central to the pathogenesis of these conditions is the inflammatory response-a key defense mechanism that, when dysregulated, accelerates disease progression and disrupts cellular homeostasis, ultimately leading to adverse clinical outcomes. Efficient resolution of inflammation is essential not only for halting the inflammatory responses but also for restoring tissue integrity. One critical aspect of resolving inflammation is the efficient clearance of apoptotic cells, a process known as \"efferocytosis,\" which remains underappreciated. Cardiac macrophages are tasked with removing apoptotic cells, necrotic cells, and cellular debris through efferocytosis. Importantly, recent studies have demonstrated that efficient efferocytosis is associated with improved outcomes in CVDs, whereas impaired efferocytosis perpetuates inflammation and hinders recovery. This tightly regulated mechanism not only resolves inflammation by suppressing proinflammatory cytokines but also stimulates the production of anti-inflammatory cytokines and reprograms macrophages to promote tissue homeostasis. This mini-review consolidates current understanding of macrophage efferocytosis and its molecular mechanisms, providing valuable insights into cardiac health and highlighting its significant potential as a therapeutic avenue for treating CVDs.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 SI","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12955849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147349999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}