ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1635178
This article is part of the Research TopicImmunomodulatory Strategies in Perioperative Organ Protection: From Mitochondrial Dysfunction to Clinical ApplicationsView all articles
Spatiotemporal Regulation of Ventilator Lung Injury Resolution by TGF-β1+ Regulatory B Cells via Macrophage Vesicle-Nanotherapeutics
Provisionally accepted
- 1Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- 2Guangxi Maternal and Child Health Hospital, Nanning, China
- 3The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
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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 vs. controls, P < 0.001; PV10d resurgence) coinciding with peak injury. TMNP administration induced sustained TGF-β1 bioavailability (PV10d: 3.6-fold vs. free cytokine, P < 0.001), attenuating histopathology (22.5% reduction in alveolar hemorrhage, P < 0.01) and suppressing IL-6/TNF-α (P < 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.
Keywords: Transforming growth factor-β1, regulatory B cells, nanoparticles Abbreviations AEC-II, type II alveolar epithelial cells, ALI, Acute Lung Injury, APC, allophycocyanin, ARDS, acute respiratory distress syndrome, BALF, bronchoalveolar lavage fluid, Breg, regulatory B cells
Received: 26 May 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Jing, Liao, Mo, He, Xie, Hu and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Linghui Pan, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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