被撤回的出版物: Overexpression of TGFβ1 in murine mesenchymal stem cells improves lung inflammation by impacting the Th17/Treg balance in LPS-induced ARDS mice (Retracted article. See vol. 13, 2022)

BackgroundT helper 17 cells (Th17)/regulatory T cells (Treg), as subtypes of CD4(+) T cells, play an important role in the inflammatory response of acute respiratory distress syndrome (ARDS). However, there is still a lack of effective methods to regulate the differentiation balance of Th17/Treg. It was proven that mesenchymal stem cells (MSCs) could regulate the differentiation of CD4(+) T cells, but the mechanism is still unclear. TGF beta 1, a paracrine cytokine of MSCs, could also regulate the differentiation of Th17/Treg but is lowly expressed in MSCs. Therefore, mouse MSCs (mMSCs) overexpressing TGF beta 1 were constructed by lentivirus transduction and intratracheally transplanted into LPS-induced ARDS mice in our study. The aim of this study was to evaluate the therapeutic effects of mMSCs overexpressing TGF beta 1 on inflammation and immunoregulation by impacting the Th17/Treg balance in LPS-induced ARDS mice.MethodsmMSCs overexpressing TGF beta 1 were constructed using lentiviral vectors. Then, mouse bone-marrow-derived MSCs (mBM-MSC) and mBM-MSC-TGF beta 1 (mBM-MSC overexpressing TGF beta 1) were transplanted intratracheally into ARDS mice induced by lipopolysaccharide. At 3 and 7 days after transplantation, the mice were sacrificed, and the homing of the mMSCs was assayed by ex vivo optical imaging. The relative numbers of Th17 and Treg in the lungs and spleens of mice were detected by FCM. IL-17A and IL-10 levels in the lungs of mice were analysed by western blot. Permeability and inflammatory cytokines were evaluated by analysing the protein concentration of BALF using ELISA. Histopathology of the lungs was assessed by haematoxylin and eosin staining and lung injury scoring. Alveolar lung fibrosis was assessed by Masson's trichrome staining and Ashcroft scoring. The mortality of ARDS mice was followed until 7days after transplantation.ResultsThe transduction efficiencies mediated by the lentiviral vectors ranged from 82.3 to 88.6%. Overexpressing TGF beta 1 inhibited the proliferation of mMSCs during days 5-7 (p<0.05) but had no effect on mMSC differentiation or migration (p>0.05). Compared to that in the LPS+mBM-MSC-NC group mice, engraftment of mMSCs overexpressing TGF beta 1 led to much more differentiation of T cells into Th17 or Treg (p<0.05), improved permeability of injured lungs (p<0.05) and ameliorative histopathology of lung tissue in ARDS mice (p<0.05). Moreover, IL-17A content was also decreased while IL-10 content was increased in the LPS+mBM-MSC-TGF beta 1 group compared with those in the LPS+mBM-MSC-NC group (p<0.05). Finally, mMSCs overexpressing TGF beta 1 did not aggravate lung fibrosis in ARDS mice (p>0.05).ConclusionMSCs overexpressing TGF beta 1 could regulate lung inflammation and attenuate lung injuries by modulating the imbalance of Th17/Treg in the lungs of ARDS mice.