scholarly journals Overexpression of TGFβ1 in murine mesenchymal stem cells improve the lung inflammation via impacting Treg/Th17 balance in LPS-induced ARDS mice

2020 ◽  
Author(s):  
Jianxiao Chen ◽  
Xiwen Zhang ◽  
Jianfeng Xie ◽  
Ming Xue ◽  
Ling Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Cd4 T Cells ◽  
Lung Inflammation ◽  
Relative Number ◽  
Lentiviral Vectors ◽  
Therapeutic Effects ◽  
T Helper 17 ◽  
Lung Injuries

Abstract Background: T helper 17 cells (Th17)/ regulatory T cells (Treg), as subtypes of CD4+T cells, played 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 proved that mesenchymal stem cells (MSCs) could regulate the differentiation of CD4+T cells, but the mechanism was still unclear. TGFβ1, as one of the paracrine cytokines of MSCs, could also regulate the differentiation of Th17/Treg but possess low expression in MSCs. Therefore, mouse MSCs (mMSCs)overexpressing TGFβ1 was constructed by lentivirus transfection and intratracheally transplanted into LPS-induced ARDS mice in our study. And the aim of which was to evaluate the therapeutic effects of mMSCs overexpressing TGFβ1 on inflammation and immunoregulationvia impacting Th17/Treg balance inLPS-induced ARDS mice. Methods: mMSCs with TGFβ1 overexpression were constructed using lentiviral vectors. Then mBM-MSCs and mBM-MSC-TGFβ1 (mMSCs overexpressing TGFβ1) were transplanted intratracheally into the ARDS mice induced by lipopolysaccharide. At 3d and 7d after transplantation, mice were sacrificed and the histopathology of lungs was assessed by hematoxylins and eosin staining and lung injury scoring. Homing of the mMSCs were assayed by ex vivooptical imaging. The relative number of Th17 and Treg in the lungs and spleens in mice were detected by FCM. IL-17A and IL-10 in the lungs of mice were analyzed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar Lung fibrosis was assessed by Masson’s trichrome staining and Ashcroft scoring. The mortality of ARDS mice was followed until 7 days after transplantation. Results: The transduction efficiencies mediated by the lentiviral vectors were 82.3-88.6%. Overexpressing TGF-β1 inhibited the proliferation of mMSCs during day 5-7 (p<0.05), but made no effects on their differentiation or migration (p>0.05). Compared to the LPS+mBM-MSC-NC group, mMSCs overexpressing TGFβ1 engraftment led to improved histopathology of lung tissue in ARDS mice (p<0.05), much more differentiation of mMSCs into Th17 or Treg (p<0.05) and improved permeability of injured lungs (p<0.05). Moreover, IL-17A was also decreased while IL-10 increased in the LPS+mBM-MSC-TGFβ1 group than in the LPS+mBM-MSC-NC group respectively (p<0.05).Finally, mMSCs overexpressing TGFβ1 did not aggravate the fibrosis of lungs in ARDS mice (p>0.05). Conclusion: MSCs overexpressing TGFβ1 could regulate lung inflammation and attenuated lung injuries via modulating the imbalance of Th17/Treg in the lungs of ARDS mice.

scholarly journals Overexpression of TGFβ1 in murine mesenchymal stem cells improves lung inflammation by impacting the Th17/Treg balance in LPS-induced ARDS mice

2020 ◽  
Author(s):  
Jianxiao Chen ◽  
Xiwen Zhang ◽  
Jianfeng Xie ◽  
Ming Xue ◽  
Ling Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Inflammation ◽  
Lung Fibrosis ◽  
Ex Vivo ◽  
Lentiviral Vectors ◽  
Mouse Bone Marrow ◽  
Therapeutic Effects ◽  
T Helper 17

Abstract Background: T 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. TGFβ1, a paracrine cytokine of MSCs, could also regulate the differentiation of Th17/Treg but is lowly expressed in MSCs. Therefore, mouse MSCs (mMSCs) overexpressing TGFβ1 were constructed by lentivirus transfection 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 TGFβ1 on inflammation and immunoregulation by impacting the Th17/Treg balance in LPS-induced ARDS mice.Methods: mMSCs overexpressing TGFβ1 were constructed using lentiviral vectors. Then, mouse bone-marrow-derived MSCs (mBM-MSC) and mBM-MSC-TGFβ1 (mBM-MSC overexpressing TGFβ1) were transplanted intratracheally into ARDS mice induced by lipopolysaccharide. At 3 d and 7 d 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 7 days after transplantation.Results: The transduction efficiencies mediated by the lentiviral vectors ranged from 82.3-88.6%. Overexpressing TGF-β1 inhibited the proliferation of mMSCs during days 5-7 (p<0.05) but had no effect on mMSCs differentiation or migration (p>0.05). Compared to that in the LPS+mBM-MSC-NC group mice, engraftment of mMSCs overexpressing TGFβ1 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-TGFβ1 group compared with those in the LPS+mBM-MSC-NC group (p<0.05). Finally, mMSCs overexpressing TGFβ1 did not aggravate lung fibrosis in ARDS mice (p>0.05).Conclusion: MSCs overexpressing TGFβ1 could regulate lung inflammation and attenuate lung injuries by modulating the imbalance of Th17/Treg in the lungs of ARDS mice.

scholarly journals Overexpression of TGFβ1 in murine mesenchymal stem cells improves lung inflammation by impacting the Th17/Treg balance in LPS-induced ARDS mice

2020 ◽  
Author(s):  
Jianxiao Chen ◽  
Xiwen Zhang ◽  
Jianfeng Xie ◽  
Ming Xue ◽  
Ling Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Cd4 T Cells ◽  
Lung Inflammation ◽  
Lung Fibrosis ◽  
Ex Vivo ◽  
Lentiviral Vectors ◽  
Mouse Bone Marrow ◽  
Therapeutic Effects

Abstract Background: T 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. TGFβ1, a paracrine cytokine of MSCs, could also regulate the differentiation of Th17/Treg but is lowly expressed in MSCs. Therefore, mouse MSCs (mMSCs) overexpressing TGFβ1 were constructed by lentivirus transfection 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 TGFβ1 on inflammation and immunoregulation by impacting the Th17/Treg balance in LPS-induced ARDS mice. Methods: mMSCs overexpressing TGFβ1 were constructed using lentiviral vectors. Then, mouse bone-marrow-derived MSCs (mBM-MSC) and mBM-MSC-TGFβ1 (mBM-MSC overexpressing TGFβ1) were transplanted intratracheally into ARDS mice induced by lipopolysaccharide. At 3 d and 7 d 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 7 days after transplantation. Results: The transduction efficiencies mediated by the lentiviral vectors ranged from 82.3-88.6%. Overexpressing TGF-β1 inhibited the proliferation of mMSCs during days 5-7 ( p <0.05) but had no effect on mMSCs differentiation or migration ( p >0.05). Compared to that in the LPS+mBM-MSC-NC group mice, engraftment of mMSCs overexpressing TGFβ1 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-TGFβ1 group compared with those in the LPS+mBM-MSC-NC group ( p <0.05). Finally, mMSCs overexpressing TGFβ1 did not aggravate lung fibrosis in ARDS mice ( p >0.05). Conclusion: MSCs overexpressing TGFβ1 could regulate lung inflammation and attenuate lung injuries by modulating the imbalance of Th17/Treg in the lungs of ARDS mice.

Mesenchymal Stem Cells Inhibit the Differentiation of CD4+ T Cells into Interleukin-17-Secreting T Cells

2008 ◽  
Vol 120 (3) ◽  
pp. 165-167 ◽  
Author(s):  
Eunsil Ko ◽  
Kyung-Ah Cho ◽  
Sun-Young Ju ◽  
So-Youn Woo
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Cd4 T Cells ◽  
Interleukin 17

86 IL-7-Producing Mesenchymal Stem Cells Sustain Colitogenic Memory CD4+ T Cells for the Persistence of Chronic Colitis

2010 ◽  
Vol 138 (5) ◽  
pp. S-15
Author(s):  
Yasuhiro Nemoto ◽  
Takanori Kanai ◽  
Teruji Totsuka ◽  
Tetsuya Nakamura ◽  
Ryuichi Okamoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Cd4 T Cells ◽  
Chronic Colitis ◽  
Memory Cd4 T Cells

scholarly journals Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Cells

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1660 ◽  
Author(s):  
Claudia Terraza-Aguirre ◽  
Mauricio Campos-Mora ◽  
Roberto Elizondo-Vega ◽  
Rafael A. Contreras-López ◽  
Patricia Luz-Crawford ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Cell Contact ◽  
T Helper 17 ◽  
Reduced Frequency

Mesenchymal stem cells (MSCs) exhibit potent immunoregulatory abilities by interacting with cells of the adaptive and innate immune system. In vitro, MSCs inhibit the differentiation of T cells into T helper 17 (Th17) cells and repress their proliferation. In vivo, the administration of MSCs to treat various experimental inflammatory and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and bowel disease showed promising therapeutic results. These therapeutic properties mediated by MSCs are associated with an attenuated immune response characterized by a reduced frequency of Th17 cells and the generation of regulatory T cells. In this manuscript, we review how MSC and Th17 cells interact, communicate, and exchange information through different ways such as cell-to-cell contact, secretion of soluble factors, and organelle transfer. Moreover, we discuss the consequences of this dynamic dialogue between MSC and Th17 well described by their phenotypic and functional plasticity.

scholarly journals Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

2017 ◽  
Vol 14 (4) ◽  
pp. 3541-3548 ◽  
Author(s):  
Zhou Xin Yang ◽  
Ying Chi ◽  
Yue Ru Ji ◽  
You Wei Wang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Cd4 T Cells ◽  
Human Umbilical Cord ◽  
Interleukin 9

scholarly journals IDO and CD40 May Be Key Molecules for Immunomodulatory Capacity of the Primed Tonsil-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5772
Author(s):  
Hyun-Joo Lee ◽  
Harry Jung ◽  
Dong-Kyu Kim
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
Suppressive Effect ◽  
Tnf Α ◽  
Immunomodulatory Capacity ◽  
Ifn Γ

Background: Tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have suppressive effect on T cells, yet much remains unknown about the underlying mechanisms supporting this effect. We investigated the underlying mechanism of the immunomodulatory effect of T-MSCs on immune cell proliferation and cytokine production. Methods: We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. Additionally, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. Results: T-MSCs significantly inhibited the immune cell proliferation and cytokine expression (TNF-α and IFN-γ) in the direct co-culture, but there was no suppressive effect in indirect co-culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co-expression CD40. Moreover, immune cells or CD4+ T cells showed lower TNF-α, IFN-γ, and IL-4 expression when the primed T-MSC were added; whereas those findings were reversed when the inhibitor for IDO (not IL-4) or CD40 were added. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4+ T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. Conclusions: Primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via Th1-mediated and Th2-mediated immune response.

Sign in / Sign up

Export Citation Format

Share Document