Objective To determine whether the signaling activation of
bone morphogenetic protein 2(BMP2)can induce myeloid-derived suppressor cells(MDSC)to secret
transforming growth factor β(TGF-β),further enhancing the differentiation and infiltration of regulatory T lymphocytes(Treg)into
tumor tissue. Methods The BMP2-induced
mRNA and
protein expression of TGF-β in MDSC was detected by quantitative real-time polymerase chain reaction and
enzyme-linked
immunosorbent assay(ELISA),respectively.The effect of BMP2-induced TGF-β secretion by MDSC on Treg differentiation was then determined by flow cytometry.Finally,we implanted the recombined human
bone morphogenetic protein 2(rhBMP2)
collagen gels into
tumor-burdened mice to examine the role of BMP2 in Treg differentiation via MDSC-secreted TGF-β in vivo.The
protein levels of TGF-β in peripheral blood and
tumor tissue were detected by ELISA,and the infiltration of Treg cells in
tumor tissue was detected by immunofluorescence assay. Results BMP2 up-regulated the
mRNA and
protein levels of TGF-β in MDSC in vitro.TGF-β secreted by the MDSC exposed to BMP2 treatment could induce the differentiation of Treg cells in vitro.Local implantation of rhBMP2 could increase the level of TGF-β
protein in peripheral blood and
tumor tissue of mice,further enhancing the infiltration of Treg cells into
tumors. Conclusion BMP2 signaling activation can induce the differentiation of Treg cells by promoting the secretion of TGF-β in MDSC,and subsequently promote the infiltration of Treg cells into
tumors.