Browse Articles

Revisiting Chalk-and-Board Pedagogy in Immunology Education: A Cognitive and Visual Learning Perspective 2256289

Abstract Introduction This study examines the educational value of traditional chalk-and-board teaching in immunology courses. Despite the increasing use of digital tools and multimedia platforms, the chalk-and-board approach remains effective, especially for immunology, which requires deep conceptual understanding and visual-spatial reasoning. Immunological processes–such as antigen presentation, cytokine signaling, and clonal selection–are inherently complex and benefit from real-time illustration and explanation. Drawing and writing on the board helps students engage cognitively, enabling them to follow the logical flow of ideas and retain information more effectively. Methods We at Chicago State University used appropriate surveillance methods, such as direct observation, digital monitoring, biometric sensors, and self-reporting tools. Ensured ethical practices by obtaining informed consent, protecting privacy, and maintaining transparency. Used tools such as LMS analytics, screen-monitoring software, and video analysis platforms to collect data. Analyzed the data using qualitative or quantitative methods. Results The results indicated that chalk-and-board teaching also enhances clarity and pacing, enabling instructors to modify explanations based on student feedback and comprehension. It reduces technological distractions and fosters active note-taking and participation. Furthermore, the visual reinforcement of cellular interactions and molecular pathways improves understanding of spatial relationships essential to immunological mechanisms. However, limitations include time constraints and decreased accessibility for students with specific needs. Conclusion This presentation advocates for reevaluating chalk-and-board teaching methods in science education, not as outdated, but as a complementary tool that enhances cognitive processing and visual learning. Future research should explore its effects on student performance, engagement, and long-term retention in immunology and other biomedical sciences. Funding Source n/a Topic Categories Immunology Education and Communication (EDU)

Bisphenol-A (BPA) exposure dysregulates wound healing in larval zebrafish 2300547

Abstract Introduction Bisphenol A (BPA), a widely used component for polycarbonate plastic production, is often found in surface water and wastewater runoff. BPA disrupts estrogen activity of humans and wildlife by binding to ERα and β, modulating both reproduction and immunity. Previously, we found BPA-exposed zebrafish larvae had decreased fin regeneration and neutrophil recruitment following a caudal fin injury. Hydrogen peroxide (H2O2) generation is tightly regulated and essential for initiation of wound healing, neutrophil migration, and regeneration. Based on work suggesting BPA upregulated NADPH oxidase in other species, we hypothesized BPA modulated H2O2 production and expression of key regeneration-related genes at the site of injury, thus affecting wound healing. Methods MPX:GFP zebrafish were continuously exposed to 100ng/ml BPA or egg water from 0-7 days post fertilization (dpf) and a caudal fin injury was induced 4 dpf. We measured H2O2 generation immediately and from 3-72 hours post-injury (hpi) in live, agarose-mounted larvae using CellMeter Hydrogen Peroxide probe and confocal microscopy. Mean fluorescence intensity was quantified using ZEN Blue image analysis. We extracted RNA from 3-72 hpi and performed qPCR to evaluate the expression of vegfa, mmp-9, tgf-beta, and il-1b; beta-actin and rpl-13a were used as reference genes. We extracted RNA from uninjured fish 2-7 dpf to assess variation in baseline expression of these genes. Results We observed an increase in H2O2 at the site of injury in BPA-treated larvae. We found BPA treatment modulated the expression of key genes involved in wound healing and tissue regeneration in response to caudal fin injury, including mmp-9. The baseline expression of mmp9 as well as most genes tested was not affected by BPA exposure, with the exception of some cytokines such as il-1b, which was more highly expressed in BPA-treated larvae. Conclusion We find that BPA exposure in zebrafish larvae dysregulated functions essential for proper wound healing. Funding Source Carleton College Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Overcoming Immunodominance by A Nanoparticle Adjuvant for Universal Influenza Vaccine Development 2255617

Abstract Introduction The immunodominance hierarchy of influenza antigens remains a major obstacle in developing broadly protective vaccines. Current flu vaccines primarily elicit antibody responses against variable head regions of hemagglutinin (HA), leading to strain-specific immunity and limited cross-protection. Cyclic dinucleotides (CDNs), potent agonists of the stimulator of interferon genes (STING) pathway, have emerged as promising adjuvants that can enhance both humoral and cellular immunity. In this study, we sought to investigate the capacity of CDN nanoparticle formulations to overcome immunodominance in influenza vaccination by combining CDN nanoparticles with influenza antigens. Methods Female C57BL/6 mice were immunized subcutaneously twice, with a 4-week interval between doses. Each group received either inactivated influenza vaccine (IIV) or hemagglutinin (HA) subunit antigen formulated with or without CDN nanoparticles. Serum samples were collected at defined time points to quantify antigen-specific IgG responses by ELISA. At the study endpoint, draining lymph nodes (inguinal lymph nodes) were harvested to assess germinal center B cell responses by flow cytometry, while bone marrow samples were collected to evaluate the frequencies of long-lived plasma cells reactive to influenza antigens by ELISpot. Results CDN nanoparticles not only enhanced the GC formation in draining lymph nodes, resulting in increased frequencies of stem-specific B cells within the GC, but also increased the frequencies of long-lived plasma cells (LLPCs) in the bone marrow. Consequently, serum antibody responses were broader and more durable. Conclusion CDN nanoparticle adjuvants broadened antibody specificity, enhanced germinal center reactions, and promoted durable long-lived plasma cell formation. This strategy overcomes the immunodominance of conventional vaccines and represents a promising approach for developing next-generation influenza vaccines with broader and longer-lasting protection. Funding Source NIH Topic Categories Vaccines and Immunotherapy (VAC)

Phospholipid Phosphatase 6 (PLPP6) protects against influenza A virus infection in mice 2305239

Abstract Introduction Phospholipid phosphatase 6 (PLPP6) is a membrane-associated enzyme that regulates polyisoprenoid diphosphate signaling in cell activation. In response to inflammatory stimuli, PLPP6 converts presqualene diphosphate to presqualene monophosphate. Because polyisoprenoids serve fundamental roles in cell immunology we aimed to investigate the role of PLPP6 in the context of influenza A virus (IAV) infection. Methods Here, we compared the immune responses between wild type (WT) and Plpp6 knockout (Plpp6-/-) mice to viral infection using a non-lethal inoculum of IAV (A/WSN/33 H1N1, 80 PFU). Methods included flow cytometry, histology and spatial transcriptomics (10x Xenium). For translation to human responses, PLPP6-siRNA was used in a human airway epithelial cell line (A549). Results Plpp6-/- mice had increased weight loss, higher viral burden, increased neutrophil and inflammatory macrophage recruitment to the lungs, and increased expression of inflammatory genes such as Isg15 and Il6 compared to wild-type controls following IAV. Spatial transcriptomic analysis revealed time dependent Plpp6 expression after IAV, in particular in lung epithelial cells during the resolution phase of IAV infection in WT mice. IAV infection of A549 cells led to significantly increased viral replication (viral titters) and burden (expression of M1 gene) after PLPP6-siRNA compared to control. Conclusion In work in progress, these findings suggest that airway epithelial PLPP6 serves in a protective role against viral infection and as a regulator of pathogen-elicited inflammation. The polyisoprenyl phosphate metabolites of PLPP6 activity that underlie this immune protection are the focus of ongoing research. Funding Source n/a Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)

Identification of latanoprost as an effective vaccine adjuvant 2309626

Abstract Introduction Identifying safe and effective vaccine adjuvants remains a critical medical challenge. Finding in-clinic small molecules with potent adjuvant properties to develop safer and more effective vaccines is an urgent need. Methods Using real time RT-qPCR, multicolor flow cytometry, a range of protein-based vaccine platforms, various immune assays, integrating model, viral and tumor antigens and applied via skin delivery to human skin explants and mouse models for discovering and evaluating potential molecular adjuvants. Results Here we identified the small molecule drug latanoprost capable of triggering a unique innate immune activation signature conducive for vaccinations in the skin including upregulated expression of proinflammatory mediators and increased frequency of migratory CD103+ conventional type 1 dendritic cells (cDC1) and plasmacytoid DC. Intradermal codelivery of latanoprost enhanced the model antigen OVA protein vaccine inducing OVA-specific IgG2c responses, which were dampened in mice that are defective in cDC1-specific IFNα/β signaling, and a higher IgG2c/IgG1 ratio. Latanoprost as an adjuvant also promoted the immunogenicity of vaccine targeting the SARS-CoV-2 Spike (S) protein by inducing long-lasting S-specific neutralizing antibodies across both sexes, but with greater effectiveness observed in males. Latanoprost-adjuvanted S protein vaccine concurrently induced S-specific polyfunctional (IFNγ+TNF+, IFNγ+IL2+) CD4 and CD8 T cells in the spleen and lung and long-lasting IFNγ+CD8 T cells in the lung of female mice, while this vaccine elicited both acute and long-lasting S-specific IL4+CD4 T cells in the spleen of male mice. Latanoprost improved the therapeutic efficacy of tumor antigen protein vaccine via skin delivery in a robust autochthonous murine melanoma model. Conclusion These findings support the translational repurposing of this in-clinic drug for ready-to-use in developing next generation clinical vaccines against cancer and infectious diseases. Funding Source NIH Topic Categories Vaccines and Immunotherapy (VAC)

A single-nucleus atlas of skeletal muscle regeneration identifies distinct macrophage populations and their cytokine environments 2257143

Abstract Introduction Skeletal muscle possesses a remarkable capacity for regeneration, a process tightly regulated by interactions between resident stem cells and the immune system. Following injury, a complex cascade of events is initiated, involving the infiltration of immune cells that clear debris and create a pro-regenerative environment. Among these, macrophages are critical mediators, exhibiting significant plasticity that allows them to switch from a pro-inflammatory to a pro-reparative phenotype. However, the full spectrum of macrophage heterogeneity and their precise communication with muscle cells remains elusive. Methods Here, we present the first single-nucleus RNA sequencing (snRNA-seq) analysis of regenerating skeletal muscle, providing an unprecedented high-resolution view of the nuclear transcriptional landscape during tissue repair. This approach overcomes the limitations of single-cell RNA sequencing (scRNA-seq) by capturing transcripts from multinucleated myofibers and minimizing cellular stress artifacts. Results Our analysis identified three distinct macrophage subpopulations with unique transcriptional and spatial profiles. We uncovered a differential regulation axis linked to CSF-1 and IL-34, where IL-34 is expressed by smooth muscle cells in proximity to resting macrophages in the perimysium and epimysium, while CSF-1 expression is transiently upregulated by fibroblasts during inflammation. Comparative analysis of aged and dystrophic (mdx and BLA/J) mouse models demonstrated a direct correlation between the degree of inflammation, the abundance of macrophage and fibroblast populations, and the expression levels of CSF-1 and IL-34. Conclusion These findings provide novel insights into macrophage heterogeneity in muscle physiology and pathology, suggesting that selectively targeting CSF-1 is a superior strategy for depleting pro-inflammatory macrophages in muscular dystrophies and age-related muscle decline. Funding Source 2021R1I1A3059820 (National Research Foundation of Korea) Topic Categories Computational and Systems Immunology (COMP)

A neuronal protein fine-tunes T cell immunity in the central nervous system 2310305

Abstract Introduction CNS autoimmune diseases such as multiple sclerosis and uveitis are driven by IL-17—producing Th17 cells, whose pathogenic conversion is promoted by IL-23 through the induction of T-bet and its downstream target IFN-γ. However, the CNS-specific signals that contribute to the pathogenic reprogramming of Th17 cells remain poorly understood. Methods We generated a dual fluorescent reporter mouse that marks the Th17 lineage and IFN-γ production to perform single-cell transcriptomic profiling of ocular T cells in experimental autoimmune uveitis (EAU). We used flow cytometry to validate candidate regulators in CNS and peripheral tissues in both wild-type and CRISPR—Cas9-engineered mice targeting genes enriched in pathogenic Th17 cells. We then evaluated disease progression in mutant mice and performed scRNA-seq analysis of ocular CD4+ T cells. We applied computational analyses to predict Th17 differentiation trajectories and disease relevance. Results Transcriptomic profiling revealed that, compared with non-pathogenic Th17 cells, pathogenic Th17 cells upregulated not only canonical inflammatory genes but also a set of neuronal genes, including neurogranin (Ng), a postsynaptic calmodulin-binding protein implicated in calcium signaling and synaptic plasticity. Using flow cytometry, we found that Ng protein is preferentially expressed by ocular Th17 cells, with minimal expression in the periphery, indicating that Ng is selectively induced in CNS-infiltrating Th17 cells. Ng-KO mice developed more severe EAU, consistent with scRNA-seq analysis of ocular CD4+ T cells showing enrichment of immune activation pathways in Ng-deficient eyes. Conclusion We propose that Ng restrains Th17 pathogenicity within the CNS, potentially by modulating TCR—driven calcium signaling. Our findings uncover an unexpected convergence of neuronal and immune programs and suggest that tissue-adapted T cells can repurpose neuronal gene networks to fine-tune local autoimmune responses in the CNS. Funding Source n/a Topic Categories Basic Autoimmunity (BA)

Fh15 Modulates Human Neutrophil Activation and Reduces NETosis 2335416

Abstract Introduction Neutrophils are essential innate immune effectors, however, excessive activation can exacerbate inflammatory disease. A key pathogenic mechanism is neutrophil extracellular traps (NETs) formation, in which neutrophils release chromatin structures with antimicrobial proteins. While NETs can aid antimicrobial defense, dysregulated NETosis amplifies inflammation, promotes endothelial/epithelial damage, and has been linked to severe outcomes in conditions such as sepsis, autoimmune disease, and acute respiratory distress syndrome. Fh15, a recombinant Fasciola hepatica fatty acid-binding protein, is a parasite-derived immunomodulator with demonstrated anti-inflammatory activity in septic shock and ulcerative colitis. Fh15 has been shown to reduce neutrophils in inflamed colonic tissue and to decrease systemic myeloperoxidase, supporting an impact on neutrophil-associated inflammation. Here, we investigate whether Fh15 directly limits NETs and modulates neutrophil activation under pro-inflammatory stimulation. Methods Primary human neutrophils were stimulated with lipopolysaccharide (LPS) and treated with Fh15 at 5, 10, or 25 µg/mL. NETs formation was quantified using 6-hour live-cell imaging. Neutrophil activation was assessed by flow cytometry based on surface expression of CD11b, CD62L, and CD16. Results Fh15 reduced NETosis at 10 (p < 0.001) and 25 (p < 0.0001) µg/mL. Flow cytometry analysis showed that LPS reduced CD11b+CD16+ neutrophils (p < 0.0001), consistent with inflammation-associated shedding or downregulation of surface CD16. In contrast, Fh15 treatment increased the percentage of CD11b+CD16+ cells compared with LPS alone (p < 0.001). Conclusion Together, the data suggests that Fh15 helps preserve surface CD16 under pro-inflammatory stimulation. In conclusion, Fh15 dampens LPS-driven neutrophil effector responses, particularly NETs formation, and may modulate activation-associated phenotypes, supporting its potential as an immunomodulatory strategy to limit neutrophil-mediated tissue damage. Funding Source Funding was provided by the RCMI-CRRGMG (U54MD007579) and PR-INBRE DRPP (2P20GM103475-02). Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Elephant‐Skin‐Inspired Porous Cementitious Tiles with Programmable Crack Networks for Passive Cooling (Adv. Mater. 44/2026)

Bilirubin alleviates cigarette smoke extract-induced lung tissue inflammation and damage by suppressing macrophage pyroptosis

Antibiotic use in early life subsequently impairs MAIT-cell mediated immunity 2256328

Abstract Introduction The use of antibiotics in early life is associated with recurrent respiratory infections in children. However, the mechanisms behind increased susceptibility to infection remain unclear. The development of mucosal associated invariant T (MAIT) cells is dependent on the recognition of derivatives of riboflavin produced by microbes during early life. Therefore, we hypothesized that use of antibiotics during this period would deplete microbes that synthesize these metabolites and disrupt MAIT cell development and related immunity to infections. Methods In vitro screening of antibiotics that are frequently prescribed to human neonates was used to identify drugs which inhibit the growth of riboflavin-synthesizing commensal bacteria. Antibiotics were administered to mice during specific developmental windows to identify the impact on MAIT cell abundances at barrier tissues and in the thymus. Infection models with Francisella tularensis were utilized to characterize the effect of impaired MAIT cell development. Models of probiotic therapy and adoptive cell transfer were explored as means to restore MAIT cell-mediated immunity. Results Administration of antibiotics to mice revealed a specific window when MAIT cell development is most affected by the depletion of riboflavin-synthesizing commensals. This resulted in a long-lasting reduction in MAIT cell abundance and an increased susceptibility to pneumonia, similar to what was observed in MAIT cell-deficient Mr1−/− mice, indicating the adverse impact on immunity is mediated by MAIT cells. Impaired MAIT cell development and immune responses were rescued by concomitant delivery of a probiotic during antibiotic treatment in early life or adoptive transfer of MAIT cells. Conclusion This work establishes a mechanism by which temporary disruption of the developing microbiome affects immune responses to infections later in life, highlighting the need for discriminant use of antibiotics and optimized probiotic therapies. Funding Source National Institutes of Health (K22AI146217, R21AI171697, & R35GM151347), National Science Foundation (Graduate Research Fellowship) Topic Categories Mucosal and Regional Immunology (MUC)

NOD1, but not NOD2, provides protection from systemic Listeria monocytogenes infection 2260383

Abstract Introduction Listeria monocytogenes (Lm) is a foodborne pathogen that can breach intestinal barriers and disseminate systemically, leading to sepsis and death in vulnerable hosts. Hospitalized cases of listeriosis carry mortality rates approaching 50%. While adaptive immunity to Lm has been well characterized, early cytosolic sensing mechanisms that limit bacterial spread remain poorly understood. The innate immune receptors NOD1 and NOD2, along with their adaptor kinase RIPK2, detect bacterial peptidoglycan and initiate protective signaling. Although individual studies have implicated NOD1, NOD2, or RIPK2 in Listeria infection, their relative contributions and interdependence during systemic disease remain unclear. Methods We used C57BL/6 mice lacking NOD1, NOD2, RIPK2, or its kinase activity to evaluate survival, bacterial burden, and cytokine responses after systemic Listeria infection. Macrophage signaling and infection-induced cell death were assessed by immunoblotting and flow cytometry. Results Our findings show NOD1 is required for survival during systemic Lm infection, whereas NOD2 is dispensable but aids recovery. Both RIPK2 KO and RIPK2 kinase-dead mice are highly susceptible to systemic Lm infection and phenocopy NOD1 KO mice. In macrophages, NOD1 and NOD2 were required for optimal activation of signaling pathways during Lm infection. Interestingly, the deficiency of NOD1 or NOD2 led to increased Lm-induced cell death in macrophages. Collectively, our results show that NOD1 and NOD2 cooperate to promote optimal innate immune responses to Lm, but NOD1 has additional nonredundant functions in vivo that are critical for host survival. Conclusion We propose that NOD1 plays distinct roles in non-immune cells, which are essential for protection, and that NOD1 regulates type I interferon production during Lm infection, a process detrimental to the host. In summary, our findings identify the NOD1—RIPK2 pathway as a dominant cytosolic sensor axis conferring protection against systemic Listeria infection. Funding Source n/a Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Loss of the Y chromosome evokes extrinsic extramedullary myelopoiesis via genome-wide epigenetic reprogramming of bladder cancer tumor cells 2255981

Abstract Introduction Loss of the Y chromosome (LOY) is a prevalent chromosomal alteration occurring in a substantial proportion of male patients with cancer including advanced bladder cancer (BLCA). Furthermore, LOY predicts reduced survival and terminal T cell exhaustion. However, the mechanisms underlying the profound immunological impacts of LOY remain unclear. Thus, the overarching rationale of this study is to define the tumor intrinsic and extrinsic drivers of immune reprogramming in LOY BLCA in order to develop targeted interventions. Methods Utilizing spectral flow cytometry, ATACseq, transcriptomic immunophenotyping, chemokine array profiling, adoptive cellular transfer and transgenic murine models we interrogated how LOY in cancer cells provokes immune dysfunction. Results Herein, we report that LOY in cancer cells provokes systemic, suppressive programming of monocyte derived macrophages via epigenetic derepression of aminopeptidase, ANPEP. Functionally, LOY induces loss of Y-encoded histone lysine demethylases KDM5D and UTY, culminating in a genome-wide shift in the epigenetic landscape of tumor cells. LOY or targeted deletion of KDM5D or UTY evoked ANPEP upregulation and ANPEP-driven accumulation of CCR2+ monocyte-derived macrophages via extramedullary myelopoiesis. Intercepting myeloid recruitment via CCR2 blockade, macrophage depletion or ANPEP ablation reduced LOY tumor growth. Inversely, enforced ANPEP expression in Y competent tumors promoted tumor progression, splenic expansion and macrophage accumulation. These findings highlight the protumor role of LOY and identify ANPEP/CCR2-axis signaling as therapeutic targets in BLCA while delineating a relationship between LOY and ANPEP in other solid tumors Conclusion Our results (1) elucidate the overarching role of the Y chromosome in shaping genome wide transcriptional accessibility via regulation of histone methylation and (2) substantiate how LOY coordinates profound immunological impacts in BLCA via chemokine-dependent myeloid reprogramming. Funding Source P01 CA278732/CA/NCI NIH HHS/United States Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Humanized B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice Model for Efficacy and Toxicity Evaluation 2302190

Abstract Introduction The IL-4 receptor (IL4RA) is a key mediator of the signaling pathways for both IL-4 and IL-13, which play pivotal roles in the pathophysiology of type 2 inflammatory diseases. Thymic stromal lymphopoietin (TSLP) is an alarmin cytokine derived from epithelial cells that has the capacity to initiate both type 2 and non-type 2 inflammatory responses in asthma. TSLP is closely associated with the production of T helper (Th) 2 cytokines, such as IL-4, and is implicated in various inflammatory conditions, including asthma and atopic dermatitis. By simultaneously targeting IL4RA and TSLP, there is significant potential to concurrently suppress both type 2 and non-type 2 inflammation, potentially yielding synergistic effects that inhibit type 2 inflammation more effectively. This therapeutic strategy is anticipated to offer enhanced efficacy in the treatment of type 2 inflammatory diseases. Methods However, TSLP and IL-4 do not cross-react with their receptors between humans and mice. To address this issue, we developed the humanized B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice model for in vivo efficacy evaluation. Results The humanized mice exhibit characteristics that closely resemble those of wild-type mice, including body weight, blood biochemical indices, and routine blood parameters. The stability of these fundamental physiological indices provides a critical assurance for safety evaluations. In the asthma model developed in B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice, we observed elevated levels of eosinophils, IgE production, and distinct lung pathological features. Notably, the combination of anti-IL4RA and anti-TSLP antibody therapies demonstrated enhanced therapeutic efficacy compared to administering a single antibody drug alone. Conclusion In conclusion, the humanized B-hIL4/hIL4RA/hTSLP/hTSLPR plus mice model serves as an excellent platform for assessing the efficacy and safety of human IL-4RA and TSLP-related antibodies. Funding Source N/A Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

High-Dose Influenza Vaccination Partially Restores Impaired T Follicular Helper Cell Function in Aging and HIV 2309758

Abstract Introduction We have previously noted that flu vaccine responses decline with aging and further impaired in people with HIV (PWH), linked to chronic inflammation and impaired peripheral T follicular helper cell (pTfh) function. This study evaluated young (Y) and old (O) virally suppressed people with HIV (PWH) and people without HIV (PWoH) to determine whether high-dose (HD) vaccination could overcome pTfh defects. Methods Participants (mean age, n) included YPWH (33, n = 10), OPWH (65, n = 19), YPWoH (31, n = 10), and OPWoH (65, n = 19), who received a standard-dose (SD) influenza vaccine in one season followed by HD the next. PBMC at D0 and D14 were stimulated with A/H1N1 for 12h and stained (surface/ICS) to identify Activation Induced Markers (AIM) CD40L and CD69 in pTfh (CD45RO+CXCR5+ PD-1hi)) CD4+ T cells and intracellular cytokines by high-dimensional flow cytometry. Serum A/H1N1 and whole-vaccine (WV) HAI titers were measured at D0 and D28. Results With SD, A/H1N1 D28/D0 titer fold change (FC) was higher in PWoH than PWH. H1N1-induced AIM+ pTfh frequencies did not differ across groups at D0 or D14 post-SD vaccine. In AIM+ pTfh cells at D14, intracellular IL-21 was similar between groups, but IL-2 and TNF-α (deleterious for Ab production) were higher in O vs Y participants. In OPWH, TNF-α at D14 negatively correlated with WV titer FC (r=-0.78, p = 0.04). In YPWoH, ICOS expression increased and the Th2 marker CCR6 was reduced in AIM+ pTfh cells from D0 to D14. In YPWH, HD increased pTfh frequencies at D14 verse SD and correlated with WV (r = 0.64, p = 0.046) and H1N1 titer FC (r = 0.71, p = 0.002). HD vaccination lowered IFN-γ and IL-2 in AIM+ pTfh cells versus SD among Y participants, while O participants increased ICOS expression that correlated with WV (r = 0.74, p = 0.002) and H1N1 titer FC (r = 0.54, p = 0.036) in OPWH. Conclusion HD vaccination increased AIM+ pTfh frequency, enhanced ICOS expression and reduced pro-inflammatory cytokine production in pTfh with improved vaccine responses in aging individuals and PWH. Funding Source R01AG068110 to S. Pahwa and S. Pallikkuth (MPI) Topic Categories Immune Mechanisms of Human Disease (HUM)

Location-directed functions of CD11c in regulating B cell tolerance 2259136

Abstract Introduction Autoimmunity, aging and infection drive aberrant accrual of CD11c+ B cells. CD11c (integrin α ITGAX), is classically defined as a dendritic cell marker and functions as both a complement receptor (CR4) and an integrin. However, its characterization on B cells remain limited. Single nucleotide polymorphisms near ITGAX locus have been identified as risk alleles for systemic lupus erythematosus (SLE), and patients with severe SLE exhibit marked expansion of CD11c+ B cells. These findings underscore the need to define B cell-intrinsic functions of CD11c in autoimmunity. Given the debated functional and developmental heterogeneity within CD11c+ B cells, we hypothesized that CD11c exerts multifaceted roles in maintaining B cell tolerance and homeostasis. Methods Using adoptive transfer and mixed bone marrow chimera models with CD11c deficient mice, we identified CD11c as a potential checkpoint of B cell tolerance. Results B cell-intrinsic CD11c deficiency impaired mature B cell recirculation to the bone marrow yet promoted spontaneous autoreactive germinal center development and autoantibody production within the autoimmune milieu of global CD11c deletion. We propose that CD11c restricts the peripheral release of proto-autoreactive B cells, thereby serving as a central tolerance regulator. Furthermore, splenic CD11c+ B cells displayed enhanced proliferation relative to their CD11c- counterparts, underscoring the context-dependent functions of CD11c in autoimmunity. Conclusion Together, these findings reveal tissue-specific roles of CD11c in shaping B cell fate, providing new insight into mechanisms of B cell tolerance and autoimmune pathology. Funding Source Canadian Institutes of Health Research (CIHR) Doctoral Foreign Study Award 202110DFD-475148-94277; National Institutes of Health (NIH) grants R01AR074105 and R01AI130307; Lupus Research Alliance Lupus Mechanisms and Targets Award Topic Categories Basic Autoimmunity (BA)

Manganese-Polydopamine Nano-Immunomodulator Synergistically Activates the STING Pathway and Pyroptosis for Renal Cell Carcinoma Immunotherapy 2308359

Abstract Introduction Renal cell carcinoma (RCC) remains highly resistant to conventional therapies, highlighting the need for innovative treatments. Tumor-associated macrophages (TAMs) play a critical role in RCC progression by promoting immune evasion and supporting tumor growth. Manganese ions have been shown to activate the cGAS-STING pathway, enhancing anti-tumor immunity. However, precise targeting and controlled release of manganese in the tumor microenvironment remain major challenges. Methods We developed manganese-polydopamine nano-immunomodulators (PDA-Mn-HA NPs), coated with hyaluronic acid (HA), to selectively target CD44 receptors on TAMs and RCC cells. These nanoparticles were characterized for their size, surface charge, and manganese release profile. In vitro, we assessed their ability to induce M1 macrophage polarization, stimulate cytokine production, and generate reactive oxygen species (ROS). We also evaluated their potential to induce pyroptosis in RCC cells and tested their therapeutic effects in a preclinical RCC mouse model. Results PDA-Mn-HA NPs effectively induced M1 macrophage polarization, promoting the release of pro-inflammatory cytokines and chemokines crucial for immune activation. Transcriptomic analysis showed significant changes in gene expression related to immune response in macrophages, confirming the nanoparticles’ immunomodulatory role. In RCC cells, PDA-Mn-HA NPs induced ROS-mediated pyroptosis through the caspase-3/GSDME pathway, further enhancing immune system activation. In vivo, PDA-Mn-HA NPs not only inhibited RCC tumor growth but also increased immune cell infiltration, particularly cytotoxic T cells, reshaping the tumor microenvironment to promote anti-tumor immunity. Conclusion PDA-Mn-HA NPs offer a promising strategy for RCC treatment by synergistically targeting both TAMs and RCC cells. This dual action enhances anti-tumor immunity and addresses the challenges of manganese ion delivery, presenting a novel approach to RCC immunotherapy. Funding Source This work was funded by the National Natural Science Foundation of China (Grant No. 81801913) and the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2020B1515020036). Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

Neutrophil Activation Signature Associated with Pulmonary Fibrosis in Hermansky—Pudlak Syndrome Type 1 2308849

Abstract Introduction Hermansky—Pudlak Syndrome type 1 (HPS-1) is a rare lysosomal disorder in which all patients develop progressive pulmonary fibrosis. Neutrophils are increasingly recognized as drivers of epithelial injury and aberrant repair, but the systemic inflammatory signatures that distinguish fibrotic from non-fibrotic HPS remain unclear. We quantified plasma immune mediators to derive pathway-based neutrophil activation and fibrosis remodeling scores, aiming to determine whether circulating profiles reflect HPS disease phenotype and clinical severity. Methods Plasma from HPS-Fibrotic (HPS-F), HPS-Nonfibrotic (HPS-NF), Nonfibrotic Lung Disease (NFLD), and Healthy Controls (HC) was analyzed using NULISAseq™. A Neutrophil Activation Score (NAS-10) with 10 markers and a Fibrosis Remodeling Score with 8 markers for epithelial injury and profibrotic injury was computed. Group comparisons used nonparametric testing; clinical associations were assessed using Spearman correlations. Results NAS-10 was significantly higher in HPS-F compared with HPS-NF (p = 0.034) and HC (p = 0.034), indicating increased neutrophil activation in fibrotic disease. The Fibrosis Score was also significantly elevated in HPS-F relative to HC (p < 0.0001). Both indices were associated with pulmonary function, showing inverse correlations with FVC% (Fibrosis Score: r = —0.74, p = 0.046; NAS-10: r = —0.72, p = 0.037). In addition, NAS-10 correlated positively with the Fibrosis Score (r = 0.80, p = 0.014), linking neutrophil-driven inflammation with fibrotic remodeling in HPS-associated lung disease. Conclusion High-dimensional immune profiling enables the development of composite scores that discriminate fibrotic from non-fibrotic HPS and show strong associations with pulmonary function decline. Together, these findings support the use of immune signatures as tools for disease monitoring and for guiding therapeutic studies in HPS-associated pulmonary fibrosis. Funding Source Research Centers in Minority Institutions (RCMI) Center for Research Resources Grant and the Molecular and Genomics Core (#U54MD007579), PR-INBRE Developmental Research Project Program (DRPP) (#5P20GM103475-21). Graham Grant. Topic Categories Immune Mechanisms of Human Disease (HUM)

Flexible Dielectric Acoustic Resonator Patch for Tissue Regeneration (Adv. Mater. 43/2026)

Hybrid Amyloid–Boron Nitride Aerogels for Lightweight Sound Insulation

ABSTRACT Boron nitride (BN) is a lightweight, thermally stable, and chemically inert material widely used in electronics and insulation, yet its synthesis typically relies on energy‐intensive, high‐temperature routes. Here, we introduce a sustainable, bottom‐up strategy to fabricate hybrid boron nitride–amyloid fibril (BNAF) aerogels, in which whey protein amyloid fibrils serve as renewable scaffolds that assist the organization of BN‐rich domains. A mild ultrasonication–freeze‐drying process yields ultralight aerogels with hierarchical porosity, increased BN‐like ordering relative to the protein‐free control, and fibril‐induced reinforcement. The hybrid aerogels combine mechanical reinforcement, thermal stability under moderate‐use conditions, and strong acoustic performance, achieving sound absorption coefficients above 0.8, noise reduction coefficients up to 0.63, and sound transmission losses of 25–30 dB. This combination of low density and strong sound shielding compares favorably with common lightweight acoustic materials such as fiberglass, establishing amyloid‐assisted BN–protein hybrid aerogels as promising candidates for moderate‐temperature, weight‐sensitive noise‐reduction applications.