ArticleNature biomedical engineering2023
Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.
Article in Nature biomedical engineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
- Clinical and Immunologic Effects of Extracorporeal Cytokine Removal in Patients with Septic Shock: A Randomized Controlled Trial.Shock (Augusta, Ga.) · 2026Trial
- Lactococcus lactis NZ3900/pNZ8149-ChIL-4-ChIL-2 alleviates compound stress in chicks via reshaping immune homeostasis, gut microbiota and intestinal health.Poultry science · 2026Article
- A portable nanobiosensor with machine learning: enabling multi-cytokines point-of-care testing and early identification of sepsis immunoparalysis.Journal of nanobiotechnology · 2026Article
- Single-cell transcriptomic analysis reveals immune remodeling in bone marrow during aged sepsis.GeroScience · 2026Article
- Unveiling Gut Homeostasis Disruption in Sepsis: Towards an Integrated Mechanistic and Translational Roadmap.Cell proliferation · 2026Review
- Steroid hormone ouabain cooperates with NaActa pharmaceutica Sinica. B · 2026Article
- Trained immunity modulators: A new frontier in immunoregulation and disease intervention.Journal of advanced research · 2026Review
- Monocyte/macrophage-mediated trained immunity in disease prevention and immunotherapy.Bioactive materials · 2026Review
- Novel genetic insights into causal effects of potential metformin targets and immune mediation on sepsis.Biology direct · 2026Article
- Hexokinase 3 promoted cytokine production of monocytes by targeting metabolic reprogramming and histone lactylation in sepsis.Clinical epigenetics · 2026Article
- Tissue context as a determinant of trained innate immunity: a conserved molecular toolkit with divergent functional outputs.Journal of leukocyte biology · 2026Review
- Delivering cytokine mRNA to secondary lymphoid organs for robust cancer immunotherapy.Research square · 2026Article
- Bench-to-Bedside Insights into the Challenges of Immunosuppression in Sepsis.Pathogens (Basel, Switzerland) · 2026Review
- Recent perspectives on macrophage memory: types, mechanisms, and characteristics in pulmonary diseases.Cell communication and signaling : CCS · 2026Review
- Emerging Nanomedicine Strategies for Sepsis: Immunomodulation and Beyond.Research (Washington, D.C.) · 2026Article
- Trained immunity-based mucosal immunotherapies for preventing respiratory infections: a translational, evidence-graded appraisal of platforms, populations, and the protection-immunopathology balance.Frontiers in medicine · 2026Review
- Mitochondrial dysfunction in sepsis-induced immunoparalysis: from immune-cell metabolic reprogramming to clinical biomarkers.Frontiers in immunology · 2026Review
- Trained Immunity and Cardiovascular Risk: An Immunological Perspective.Immunological reviews · 2026Review
- Trained immunity and related memory responses in lung health and disease.Frontiers in immunology · 2026Review
- Lymphocyte function inhibition and exhaustion in sepsis: mechanisms and applications.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
32 authors at 7 institutions in 6 countries.
Funding
Abstract
Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.