Interleukin-10 Gene-Modified Dendritic Cell-Induced Type 1 Regulatory T Cells Induce Transplant-Tolerance and Impede Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

Wan, Jing; Huang, Fang; Hao, Siguo; Liu, Chuanxu; Zhang, Wenhao; Deng, Xiaohui; Chen, Linjun; Ma, Liyuan; Tao, Rong

doi:10.1159/000480415

Cited by 12 publications

(9 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, it was indicated that allogeneic CD4 + T-cells, including Tregs, are closely related to HSCs [10]. Tregs play a significant role in inducing peripheral tolerance to self and foreign antigens [39]. As previously reported, the xenograft survival was longer in CD4+ T-cell-depleted mice, in contrast to in CD4+ T-cell mice [40].…”

Section: /Cd8mentioning

confidence: 77%

Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells

Zhao

Shen

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Immune tolerance is considered the only way to manage liver transplantation (LT). The current study hypothesized that galectin-1 via the activation of hepatic stellate cells (HSCs) is capable of inducing immune tolerance in LT. Methods: Lentiviral-mediated gene knockdown and overexpression of galectin-1 were conducted in HSC-T6 cells. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to determine galectin-1 expression. LT was performed in 20 C57BL/J6 mice and 20 C3H mice. T-cells were assigned into control, Galectin-1 shRNA, Galectin-1 OE, Galectin-1 OE SB431542, Galectin-1 OE Sulforaphane, Galectin-1 OE Y27632, and Galectin-1 OE UO126 groups. CFSE, flow cytometry, and ELISA were respectively employed to detect T-cell proliferation, CD4⁺/ CD8⁺ ratio and IL-2, IL-10 and TGF-β levels. After establishing mouse models of immune tolerance and acute rejection, immunohistochemistry, TUNEL, and immunofluorescence assay were performed to determine CD3⁺ expression, apoptosis, α-SMA, and desmin. Mouse models of CCl4-induced liver fibrosis were established, followed by assigning the control₁ and CCl4 groups. ELISA was used to determine ALT, AST, TBIL and Hyp levels. A total of 3 C57BL/J6 mice (donor) and 6 C3H mice (recipient) were grouped into the control₂ and UO126 groups, followed by ELISA detection for IL-2, IL-10 and TGF-β. Results: In T-cells, galectin-1 shRNA increased cell proliferation and IL-2 levels with reduced IL-10 and TGF-β levels, while the Galectin-1 OE and Galectin-1 OE UO126 groups revealed the opposite results. Galectin-1 overexpression elevated the ratio of the CD4⁺ to CD8⁺ T-cells. The acute rejection group exhibited enhanced desmin expression and reduced α-SMA expression. Compared with the immune tolerance group, the acute rejection group displayed higher galectin-1 expression, a positive expression rate of CD3⁺ T-cells, and an increased apoptosis rate. Compared with the control₁ group, the CCl4 group exhibited higher galectin-1 expression, ALT, AST, TBIL, and Hyp levels, α-SMA expression and CD4⁺/CD8⁺ T-cell ratio, in addition to decreased expression of desmin. Compared with the control₂ group, UO126 increased galectin-1 expressions, IL-10 and TGF-β levels and reduced IL-2 levels with inactivated HSCs. Conclusions: The findings of the current study indicated that the overexpression of galectin-1 promoted the activation of HSCs, which reduced the inflammatory response by exerting immunosuppressive effects and accordingly contributed to immune tolerance in LT.

show abstract

Section: /Cd8mentioning

confidence: 77%

Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells

Zhao

Shen

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Anti‐inflammatory and immunosuppressive factors such as IL‐10, TGF‐β1, FasL and vitamin D3 metabolites produced by genetic modification inhibited the expression of costimulatory molecules and enhanced the tolerogenic potential of DCs to block their maturation and maintain them at the immature stage . Gene‐modified DCs can induce regulatory T cells and promote transplant‐tolerance after allogeneic transplantation . The current study manipulated imDCs to enhance immune tolerance by two mechanisms: suppressing the expression of costimulatory molecules by overexpressing IL‐10; and promoting antigen‐specific T‐cell apoptosis by overexpressing FasL.…”

Section: Discussionmentioning

confidence: 93%

Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model

Zhang

Zhu

et al. 2019

Immunol Cell Biol

View full text Add to dashboard Cite

Acute rejection is the major determinant for the long-term survival of donor liver after liver transplantation (LT). The aim of this study was to examine the therapeutic potential of interleukin (IL)-10-FasL-overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL-10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T-cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post-transplant survival. IL-10 and FasL co-transduction of imDCs induced a greater reduction in CD80, CD86 and major histocompatibility complex class II (MHC II) expression, as well as T-cell proliferation, but increased levels of IL-10 and FasL in culture supernatants compared with mono-transduced or untransduced imDCs (P < 0.05). The infusion of co-transduced imDCs in LT recipients reduced RAI scores, decreased plasma AST and TBIL, and prolonged survival compared with mono-transduced or untransduced imDC-treated liver allografts. These findings demonstrated that the transfusion of IL-10-FasL/imDCs enhanced immune tolerance and prolonged the survival of liver allografts after LT. The immunomodulatory activity of IL-10-and FasL-modified imDCs might be a new therapeutic approach to prevent organ rejection in clinical transplantation.

show abstract

“…The results demonstrate that nasal administration of EBI can induce IL‐10‒expressing DCs; these DCs are CD11c + CD25 + . Because IL‐10‒producing DCs have immune‐tolerogenic properties, this fraction of DCs may be TolDCs.…”

Section: Resultsmentioning

confidence: 99%

Probiotic extracts ameliorate nasal allergy by inducing interleukin‐35‒producing dendritic cells in mice

Xue

et al. 2019

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

Background:The therapeutic efficacy of allergic rhinitis (AR) needs to be improved. Probiotics have immunoregulatory functions. In this study we evaluated the effects of protein extracts of probiotics in the amelioration of AR.Methods: Extracts of Bifidobacterium infantis (EBI) were prepared by lysing the live probiotics. AR mice were developed to be used to evaluate the therapeutic efficacy of EBI. Results:The results show that EBI induced interleukin (IL)-10-producing dendritic cells (DCs) via increasing IL-35 and signal transducer and activator of transcription 3 (STAT3) phosphorylation. IL-10-expressing DCs induced IL-10-producing B cells (B10 cells), with the la er showing immunosuppressive functions. A er challenge with specific antigens, AR mice showed sneezing, nasal itch, and increases in serum-specific immunoglobulin E (IgE) and mouse mast cell protease-1; higher levels of T helper 2 (Th2) cytokines (IL-4, 67.17 ± 10.66; IL-5, 62.83 ± 9.70; IL-13, 51.00 ± 6.69, before treatment) in nasal mucosal protein extracts, which were significantly suppressed (IL-4, 27.00 ± 6.66; 23.86 ± 4.53;25.67 ± 4.93, a er treatment (p < 0.001) by administration with EBI nasal drops.Conclusion: EBI can suppress AR via inducing B10 cells. Thus, a er carrying out required preclinical experiments and tests, EBI has the translational potential to be used in the treatment of AR and other allergic diseases. C 2019 ARS-AAOA, LLC. How to Cite this Article:Xue J-M, Ma F, An Y-F, et al. Probiotic extracts ameliorate nasal allergy by inducing interleukin-35-producing dendritic cells in mice. Int Forum Allergy Rhinol. 2019;9: 1289-1296.A llergy (AR) is an adverse response to food antigens by the immune system in the airway mucosa. The under-

show abstract

Interleukin-10 Gene-Modified Dendritic Cell-Induced Type 1 Regulatory T Cells Induce Transplant-Tolerance and Impede Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

Cited by 12 publications

References 42 publications

Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells

Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells

Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model

Probiotic extracts ameliorate nasal allergy by inducing interleukin‐35‒producing dendritic cells in mice

Contact Info

Product

Resources

About