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Article Abstract
Background: Regulatory B cells (Breg) critically orchestrate inflammatory resolution and tissue repair. This study investigates the therapeutic potential of transforming growth factor (TGF)-β1-producing Bregs in ventilator-induced lung injury (VILI), leveraging biomimetic nanotechnology to overcome limitations of conventional cytokine delivery.
Methods: We engineered macrophage-derived microvesicle-encapsulated nanoparticles (TMNP) for pH-responsive, spatiotemporally controlled TGF-β1 release. Therapeutic efficacy was evaluated in a murine VILI model through longitudinal immunophenotyping, histopathology, and cytokine profiling at post-ventilation days 1 and 10 (PV1d, PV10d).
Results: VILI triggered biphasic pulmonary Breg expansion (PV1d: 7.83-fold . controls, < 0.001; PV10d resurgence) coinciding with peak injury. TMNP administration induced sustained TGF-β1 bioavailability (PV10d: 3.6-fold . free cytokine, < 0.001), attenuating histopathology (22.5% reduction in alveolar hemorrhage, < 0.01) and suppressing IL-6/TNF-α ( < 0.01). Treatment concomitantly expanded Breg populations and modulated T cell subset.
Conclusion: TMNP orchestrates Breg-mediated immunoresolution through precision cytokine delivery and lymphocyte modulation, enabling dual-phase protection against ventilation-associated immunopathology. This paradigm represents a transformative approach for acute respiratory distress management.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286806 | PMC |
| http://dx.doi.org/10.3389/fimmu.2025.1635178 | DOI Listing |
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