Macrophage-derived Microvesicles Coated Nanoparticles Loaded with TGF-β1 Resolve Acute Lung Injury via Regulatory B Cell Activation

Abstract

Regulatory B cells (Breg) are vital for inflammation and tissue injury resolution. Here, we investigated the role of transforming growth factor-β1 (TGF-β1)-producing Breg in the murine model of ventilation-induced lung injury (VILI). The percentages of pulmonary CD19^highCD44(+) TGF-β1(+) Breg were increased at PV1d and PV10d in VILI mice. Lung injury and inflammation were attenuated by up-regulating TGF-β1 levels with regulation of T-cell immunity. To prolong and stabilize the effect of exogenous TGF-β1, macrophage-derived microvesicles-coated nanoparticles (MNP) loaded TGF-β1(TMNP) were synthesized, and VILI mice were divided into sham, recombinant TGF-β1 (rTGF-β), MNP, and TMNP groups. TMNP increased the TGF-β1 levels in serum and lung tissues at PV10d. Compared with rTGF-β group, lung injury and inflammation in TMNP group at PV1d were attenuated with Breg proliferation; TMNP induced the reduction of pulmonary CD4(+) T cell proportions and CD4(+)/CD8a(+) T cell ratios, but promoted the proliferation of pulmonary CD8a(+) T cells at PV1d and PV10d. Together, TMNP promote the resolution of inflammatory lung injury, which may be associated with the proliferation of Breg to maintain immunological homeostasis.