High-throughput screen identifies non inflammatory small molecule inducers of trained immunity

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(29)

Опубликована: Июль 8, 2024

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result increased cytokine effector responses pathogenic challenges, providing nonspecific protection against disease. It may also improve immune established immunotherapeutics vaccines. Despite its promise for next-generation therapeutic design, most current understanding experimentation conducted with complex heterogeneous biologically derived molecules, such as β-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. limited collection of training compounds limits study genes involved each molecule has both nontraining effects. Small molecules tunable pharmacokinetics delivery modalities would assist trained future applications. To identify small inducers immunity, we screened a library 2,000 drugs drug-like compounds. Identification well-defined our innate memory broaden scope clinical We identified over two dozen several chemical classes that induce phenotype absence initial activation—a limitation reported training. A surprising was identification glucocorticoids, traditionally considered immunosuppressive, an unprecedented link between glucocorticoids immunity. chose seven these top candidates characterize establish activity vivo. In this work, expand number known creating alternative avenues studying applying

Язык: Английский

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The Yin and Yang of TLR4 in COVID-19

Cytokine & Growth Factor Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Hematopoietic stem cell state and fate in trained immunity

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 14, 2025

Язык: Английский

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Trained immunity alleviates the progression of melanoma during sepsis-associated immunoparalysis

Cellular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Patients who survive the excessive inflammatory phase of sepsis experience prolonged immunoparalysis/immunosuppression. During this phase, patient's immune system is severely impaired, which increases susceptibility to septic complications. Sepsis survivors have a significantly greater incidence cancer, but mechanism underlying phenomenon unknown. We constructed two sepsis-melanoma models assess relationship between and sepsis-related concomitant cancer. In our investigation, we employed range experimental technique elucidate intricate mechanisms through immunoparalysis facilitates melanoma progression. Furthermore, induced trained immunity with oroxylin A (OA) evaluate its ability reverse subsequent tumor progression in models. showed that upregulated serum level interleukin (IL)-6 number myeloid-derived suppressor cells (MDSCs), regulated G-MDSCs/M-MDSCs inhibited CD8+T-cell function, promoted OA-induced can immunoparalysis, maintain antitumor capacity system, inhibit development sepsis-complicated melanoma. Notably, OA target macrophage migration inhibitory factor (MIF) downregulate IL-6, may be crucial molecular by induces sepsis. promote cancer upregulating MIF increasing ratio reducing function CD8+ T cells, leading while alleviate The findings study provide new strategies for preventing or treating

Язык: Английский

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Systems Human Immunology and AI: Immune Setpoint and Immune Health

Annual Review of Immunology, Год журнала: 2025, Номер 43(1), С. 693 - 722

Опубликована: Апрель 25, 2025

The immune system, critical for human health and implicated in many diseases, defends against pathogens, monitors physiological stress, maintains tissue organismal homeostasis. It exhibits substantial variability both within across individuals populations. Recent technological conceptual progress systems immunology has provided predictive insights that link personal states to intervention responses disease susceptibilities. Artificial intelligence (AI), particularly machine learning (ML), emerged as a powerful tool analyzing complex data sets, revealing hidden patterns biological scales, enabling models individualistic potentially personalized interventions. This review highlights recent advances deciphering variation predicting outcomes, through the concepts of setpoint, health, use system window measuring health. We also provide brief history AI; ML modeling approaches, including their applications immunology; explore potential AI develop state embeddings detect early signs disease, forecast interventions, guide strategies.

Язык: Английский

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Trained immunity-based Adjuvated vaccines (TIbAV) approach: β-glucans as example

Vaccine, Год журнала: 2025, Номер 57, С. 127240 - 127240

Опубликована: Май 1, 2025

Язык: Английский

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Trained immunity driven by Enterococcus faecalis ribosomal protein S11 enhances antigen presentation and boosts influenza vaccine efficacy via nanoparticle delivery

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 144179 - 144179

Опубликована: Май 1, 2025

Язык: Английский

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