ArticleProceedings of the National Academy of Sciences of the United States of America2023
The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Protective effect of Zymosan-A against radiation-induced premature ovarian insufficiency in a murine model.iScience · 2026Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Radiation-Induced Immune Modulation and Inflammatory Responses in Human Cells and Tissues.International journal of molecular sciences · 2026Review
- Can Phagocytosis, Neutrophil Extracellular Traps, and IFN-α Production in Systemic Lupus Erythematosus Be Simultaneously Modulated? A Pharmacological Perspective.International journal of molecular sciences · 2026Review
- TLR2 agonism suppresses myeloid leukemogenesis by reprogramming leukemia stem cells.Blood advances · 2025Article
- The Wake Forest Nonhuman Primate Radiation Late Effects Cohort.Radiation research · 2025Article
- FSL-1 Pre-Administration Protects Radiation-Induced Hematopoietic Organs Through the Modulation of the TLR Signaling Pathway.International journal of molecular sciences · 2025Article
- Diprovocim protects against the radiation-induced damage via the TLR2 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death.Immunological reviews · 2025Review
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided MyD88-dependent mitigation of hematopoietic acute radiation syndrome (H-ARS) in mice. Although mice and humans differ in TLR number, expression, and function, nonhuman primate (NHP) TLRs are like those of humans; therefore, studying both animal models is critical for drug development. The objectives of this study were to determine the efficacy of FSL-1 on hematopoietic recovery in small and large animal models subjected to sublethal total body irradiation and investigate its mechanism of action. In mice, we demonstrate a lack of adverse effects, an easy route of delivery (subcutaneous) and efficacy in promoting hematopoietic progenitor cell proliferation by FSL-1. NHP given radiation, followed a day later with a single subcutaneous administration of FSL-1, displayed no adversity but showed elevated hematopoietic cells. Our analyses revealed that FSL-1 promoted red blood cell development and induced soluble effectors following radiation exposure. Cytologic analysis of bone marrow aspirates revealed a striking enhancement of mononuclear progenitor cells in FSL-1-treated NHP. Combining the efficacy of FSL-1 in promoting hematopoietic cell recovery with the lack of adverse effects induced by a single administration supports the application of FSL-1 as a viable countermeasure against H-ARS.
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