ImmunoHorizons最新文献

{"title":"Teaching immunity: A blueprint for medical education.","authors":"Bonnie N Dittel","doi":"10.1093/immhor/vlag057","DOIUrl":"https://doi.org/10.1093/immhor/vlag057","url":null,"abstract":"","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149279133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of CD38 promotes severe allergic airway inflammation and hyperresponsiveness in mice.","authors":"Maria L Ford, Michelle M Rohlfing, Terri A Harshman, Kathryn M Heyob, Syed-Rehan A Hussain, Brandon W Lewis, Mitchell H Grayson, Rodney D Britt","doi":"10.1093/immhor/vlag055","DOIUrl":"https://doi.org/10.1093/immhor/vlag055","url":null,"abstract":"<p><p>Cluster of differentiation 38 (CD38) is an enzyme that is expressed by immune cells and airway smooth muscle cells and is known to regulate nicotinamide adenine dinucleotide (NAD+) metabolism and inflammation. Studies have shown that CD38 increases airway hyperresponsiveness (AHR) in mice administered acute cytokine and allergen challenge, yet its role in chronic severe allergic airway inflammation is not known. In this study, we intranasally challenged wild-type (Cd38+/+) and homozygous Cd38 (Cd38-/-) knockout mice with phosphate-buffered saline (PBS) or mixed allergens (Alternaria alternata extract, Aspergillus fumigatus extract, Dermatophagoides pteronyssinus (house dust mite) extract, and ovalbumin) and bis-(3'-5')-cyclic dimeric guanosine monophosphate (MA+GMP) for four weeks. We measured AHR to methacholine using the flexiVent system, pro-inflammatory cytokine levels in bronchoalveolar lavage fluid by ELISA, and lung innate and adaptive immune cell populations by flow cytometry. Upon MA+GMP challenge, we observed that Cd38-/- mice have significantly higher AHR compared to Cd38+/+ mice. Interestingly, Cd38-/- mice challenged with MA+GMP had altered lung immune cell composition with greater type 2 innate lymphoid cells and eosinophils and less interferon-gamma producing natural killer cell populations compared to Cd38+/+ mice. These data suggest a key role for CD38 in negatively regulating type 2 inflammation, offering a novel role for CD38 in severe allergic inflammation.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149291329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex hyperspectral IHC: A 12-plex assay for high-dimensional analysis of the tumor microenvironment.","authors":"Kouther Noureddine, Paul Gallagher, John English, Jagoda Korbelik, Anita Carraro, Sylvia Lam, Puneet Arora, Athena Li, Martial Guillaud, Anna McGuire, Calum MacAulay","doi":"10.1093/immhor/vlag054","DOIUrl":"10.1093/immhor/vlag054","url":null,"abstract":"<p><p>The immune component of the tumor microenvironment (TME) is highly prognostic of patient outcome, further understanding of TME and the spatial organization of the immune cells within the TME is needed for better patient prognosis and treatment planning. Current brightfield immunohistochemistry techniques quantify immune cell counts and density but generally cannot assess the spatial relationship between tumor and immune cells due to the limited number of markers on a single slide. Here, we present a brightfield-based multiplexed immunohistochemistry workflow that combines multiple labels per staining round with iterative cycles of staining, destaining, and hyperspectral imaging to enable high-dimensional immune profiling within a single tissue section. This approach is directly compared with a sequential immunofluorescence technique applied to adjacent tissue sections to compare and evaluate its performance. By integrating serial imaging, sequential labeling, and image registration, we are able to spatially map the TME using standard brightfield microscopy.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198739","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":"Integrative scRNA-seq and scTCR-seq analyses decode dual TCR γδ T-cell characteristics in human and mouse.","authors":"Huifang Wang, Yuanyuan Xu, Naixin Cao, Qingqing Ma, Jun Li, Kai Quan, Xinsheng Yao","doi":"10.1093/immhor/vlag044","DOIUrl":"10.1093/immhor/vlag044","url":null,"abstract":"<p><p>The clonal selection theory of \"one lymphocyte expresses one type of antigen receptor\" has been challenged and complemented by the concept of dual receptor lymphocytes. However, the proportion, source, and characterization of dual TCR γδ T cells have not been determined. Using single-cell RNA plus single-cell TCR sequencing, we discovered a high proportion of dual γδ T cells datasets of the human thymus and mouse spleens. We observed differences in the proportion of single and dual TCR from γδ T cells, the types of δ and γ pairings, the frequency of TRDV and TRGV genes, and the expression of mRNA molecules across various γδ T-cell subgroups. Additionally, we investigated the likely genesis of dual TCR mRNA based on its compositional properties. This work provides a new perspective and scheme for the study of γδ T cells.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027203","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":"Beyond PD-L1/PD-1: expression of PVR/TIGIT and TNFRSF14/BTLA axes in response to Helicobacter pylori and in gastric cancer lesions.","authors":"Lucía Figueroa-Protti, Giovanna Mainieri-Breedy, Vanessa Ramírez-Mayorga, Javier Mora, Silvia Molina-Castro, Warner Alpízar-Alpízar","doi":"10.1093/immhor/vlag048","DOIUrl":"10.1093/immhor/vlag048","url":null,"abstract":"<p><p>Gastric cancer (GC) has a high mortality rate worldwide, mainly due to late detection and lack of effective treatments. Immune checkpoint (ICs) inhibitors have revolutionized cancer treatment; however, a substantial percentage of patients with GC do not respond to this treatment, which may be related to aspects underlying the conformation of the immune microenvironment during tumor development and progression. In this study, we assessed the role of Helicobacter pylori, the most recognized GC risk factor, in the concomitant induction of PD-L1, B7-H3, PVR, TNFRSF14, Gal-3, and Gal-9 in vitro. We also analyzed the expression of selected IC ligand-receptor axes in human GC lesions. The mRNA relative expression of PD-L1, PVR, and TNFRSF14 was significantly upregulated in human cell lines challenged with the bacterium. This was CagPAI dependent and further enhanced by PBMCs. In GC lesions, mRNA levels in the PVR/TIGIT and TNFRSF14/BTLA axes were higher than in the PD-L1/PD-1 axis. When the protein levels of these ICs axes were determined by flow cytometry on the different cell subpopulations of the tumor microenvironment, Tregs emerged as the lymphoid subpopulation contributing the most to the expression of PD-1, TIGIT, and BTLA receptors; their ligands were mainly expressed by GC cells. Our results suggest that, in addition to the PD-L1/PD-1 axis, PVR/TIGIT and TNFRSF14/BTLA axes may play a role in establishing an immunosuppressive microenvironment during GC development and progression. This study also highlights the potential relevance of Tregs as active players in shaping and maintaining an immunosuppressive milieu in GC lesions, in part through expression of ICs.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027164","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":"SERPINB1 as a critical regulator of inflammation and protease activity in human monocytic cells.","authors":"Jareb J Pérez-Caraballo, Xiang Ye, Jian Cui, Rubén Martínez-Barricarte","doi":"10.1093/immhor/vlag053","DOIUrl":"10.1093/immhor/vlag053","url":null,"abstract":"<p><p>SERPINB1, a member of the serpin superfamily, functions primarily as a serine protease suicide inhibitor via its reactive center loop (RCL). While murine studies have elucidated its role in neutrophil homeostasis and survival, the functions and pathways orchestrated by human SERPINB1, particularly in monocytes, remain largely undefined. Here, we demonstrate that SERPINB1 is under purifying selection, indicative of an essential, non-redundant role in human immunity comparable to that of genes known to cause immune diseases when mutated. Flow cytometric and Western blot analyses reveal ubiquitous expression in immune cells, with monocytes exhibiting the highest levels and the most active utilization of SERPINB1. Using CRISPR/Cas9-mediated knockout in THP-1 monocytic cells, we found that SERPINB1 deficiency does not impair cell viability but significantly enhances proinflammatory responses, notably increasing IL-1β production in response to lipopolysaccharide stimulation. Bulk RNA sequencing corroborated upregulation of inflammatory genes, while activity-based proteomic profiling uncovered broad alterations in enzymatic activity, affecting pathways beyond protease regulation, including ribosomal function and cellular metabolism. These findings suggest that human SERPINB1 extends its function beyond protease inhibition to modulate monocyte inflammatory activation and metabolic processes. Further mechanistic investigations are warranted to delineate the molecular interactions underpinning SERPINB1's regulatory network in monocytes. Yet, our study provides novel insights into SERPINB1's multifaceted functions in human immunity and highlights its potential as a therapeutic target for controlling dysregulated inflammation.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042956","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":"Evaluating novel antibodies for cytokine profiling in the guinea pig model.","authors":"Lea Maristela, Alyssa Longworth, David F Ackart, Faye Lanni, Joseph Gibb, Ashley Freedman, Olivia R Miller, Ling Cai, Hong Qi, Susan L Baldwin, Sasha E Larsen, Carolina Mehaffy, Marcela Henao-Tamayo, Rhea N Coler, Brendan K Podell","doi":"10.1093/immhor/vlag051","DOIUrl":"10.1093/immhor/vlag051","url":null,"abstract":"<p><p>The guinea pig model of Mycobacterium tuberculosis (Mtb) infection offers distinct advantages compared to conventional mouse models. Namely, the guinea pig model develops circumscribed granulomas with central necrosis which most closely resembles that of human granulomas. However, a limitation of this model is the lack of available reagents to characterize the Mtb immune response. To better leverage this representative model, a set of recombinant rabbit monoclonal antibodies targeting guinea pig cytokines were generated and validated. Using established stimulation conditions for primary guinea pig cells capable of producing specific cytokine profiles, the reactivity and specificity of these antibodies to their biological target were evaluated. These antibodies were then evaluated individually for direct ELISA and immunohistochemistry or part of a pair for sandwich ELISA and ELISpot techniques. Utilized in a low-dose aerosol model of Mtb in the guinea pig, the utility of these antibodies to detect specific immune cytokines generated in response to infection is demonstrated. Collectively, these antibodies will provide a more comprehensive understanding of immune kinetics, vaccine response, and comparative immunology across the guinea pig model of tuberculosis and other infectious diseases.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027257","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":"Differential peripheral immune dynamics underlie therapeutic response to chemotherapy and chemoimmunotherapy in triple-negative breast cancer.","authors":"Zahra Mesrizadeh, Kavitha Mukund, Shankar Subramaniam","doi":"10.1093/immhor/vlag049","DOIUrl":"10.1093/immhor/vlag049","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited treatment options and response to immune checkpoint inhibitors. Tumor-infiltrating lymphocytes have been extensively studied; however, the integration of peripheral immune dynamics with mechanistic regulation underlying therapeutic response remain poorly defined. Here, we integrate immune-state modeling with pathway-level mechanistic inference to analyze single-cell RNA sequencing of PBMCs from patients with advanced TNBC treated with paclitaxel alone or in combination with the anti-PD-L1 Ab atezolizumab. This framework leverages treatment arm, longitudinal sampling, and clinical response to resolve coordinated immune programs across lymphoid and myeloid compartments. We identified distinct treatment- and response-specific states before and after treatment. Chemotherapy responders displayed pretreatment adaptive immune priming, whereas combination-therapy responders exhibited preexisting effector T-cell activity coupled with tumor PD-L1 expression. In contrast, chemotherapy nonresponders developed persistent post-treatment immune dysregulation in regulatory and terminal effector programs, whereas combination-therapy nonresponders demonstrated maladaptive remodeling of adaptive and innate compartments, including dysfunctional NK and metabolically reprogrammed myeloid populations. Across regimens, pathways involving protein translation, metabolic adaptation, and stress signaling emerged as shared modulators of response. These findings suggest that coordinated adaptive-innate immune dynamics underlie therapeutic efficacy, whereas systemic immune exhaustion and myeloid immunoregulation lead to resistance. Projection of these peripheral immune programs onto independent I-SPY2 showed concordant associations with tumor immune phenotypes and pathological complete response, supporting generalizability of the findings. Our study demonstrates the utility of an integrative approach for linking peripheral immune state organization with mechanistic insights, informing response in TNBC.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027189","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":"Mostly getting along -Borrelia burgdorferi and its manipulation of the host immune system.","authors":"Shilpa Sachan, Nicole Baumgarth","doi":"10.1093/immhor/vlag052","DOIUrl":"10.1093/immhor/vlag052","url":null,"abstract":"<p><p>Lyme disease is caused when mammalian hosts not part of the sylvatic life cycle, including humans, are infected with Borrelia burgdorferi (Bb) following the bite of an Ixodes tick. Ticks and natural mammalian host reservoirs, including rodents, however, are largely disease tolerant, despite Bb establishing persistent infection. We explore the complex and ongoing interplay between Bb and the immune system. We discuss how Bb infection-induced innate responses seem maladapted to this extracellular bacterial infection, perhaps explaining why CD4+ T cells are ineffective contributors to Bb infection control. While B cell responses critically control Bb tissue burden and disease development they cannot clear the infection, showing a bias towards ongoing plasmablast responses and a lack of functional germinal centers. Identifying the mechanisms that hinder effective immune clearance of Bb may lead to new approaches for the treatment of Lyme Disease.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027217","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":"Increasing learning, confidence, and retention in the immunology classroom with LEGO.","authors":"Bernice Yphantides, Heather A Bruns, Louis B Justement, Christine Loyd, Mallary C Greenlee-Wacker","doi":"10.1093/immhor/vlag043","DOIUrl":"https://doi.org/10.1093/immhor/vlag043","url":null,"abstract":"<p><p>The process of variable-diversity-joining (V(D)J) recombination gives rise to incredible diversity in the Ab repertoire. Given its complexity, V(D)J recombination is a difficult process for undergraduates to learn. We hypothesized that modeling recombination with LEGO would increase learning gains, as well as student confidence and interest in this process. To test this, students at 3 undergraduate universities watched the same video lecture about recombination, then the LEGO modeling exercise was either demonstrated in front of students or performed by students. Students who modeled or observed modeling with LEGO performed significantly better on an exam essay question than those that opted out of the modeling exercise. Our next objective was to determine whether tactile manipulation of the model was associated with increased interest and confidence. Survey results suggested that most students preferred visual learning, followed by explanations and activities. Although most students agreed that the LEGO activity gave them more confidence and increased their interest in the material, students who did the activity were more likely to strongly agree with affirming statements. For example, students who modeled were more likely to strongly agree that the LEGO activity helped them memorize the steps of V(D)J recombination and increased their level of confidence in describing key aspects of the process. Overall, these data suggest LEGO modeling of V(D)J recombination improves student comprehension, interest, and confidence.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"10 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763285","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}