Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model

Dong, Zhiwei; Chen, Yajie; Yuan, Peng; Wang, Fan; Yang, Zichen; Huang, Guangtao; Chen, Yu; Yuan, Zhiqiang; Cao, T.; Peng, Yizhi

doi:10.1159/000477593

Cited by 15 publications

(10 citation statements)

References 29 publications

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“…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]. In the current study, the results revealed increased expression of α-SMA in CCl 4 -induced hepatic fibrosis; however, the expression of desmin was found to be decreased.…”

Section: /Cd8supporting

confidence: 74%

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

Zhao

Shen

Chen

et al. 2018

Cell Physiol Biochem

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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.

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Section: /Cd8supporting

confidence: 74%

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

Zhao

Shen

Chen

et al. 2018

Cell Physiol Biochem

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“…C-C chemokine receptor 7 (CCR7), a G protein-coupled trans-membrane protein, can promote immune cell viability and induce immune cells homing to secondary lymphoid organs following cognate ligand binding like cytokines CCL19 and CCL21 [9, 10]. Whereas the exact roles of CCR7 in disease progression and in tumor metastasis to lymphoid tissues remain controversial so far.…”

Section: Introductionmentioning

confidence: 99%

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer

Sun

et al. 2017

Cell Physiol Biochem

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Background/Aims: Previous preclinical and clinical studies have reported a positive correlation between the expression of the C-C chemokine receptor 7 (CCR7) and the incidence of lymph node metastasis in breast cancer. However, the prognostic relevance of CCR7 expression in breast cancer remains contradictory till now. The aim of this study is to assess the correlation of the CCR7 expression with other clinicopathological features and prognosis in breast cancer. Methods: The CCR7 gene amplification and mRNA expression levels from approximately 3,000 patients were retrieved from human breast cancer databases and analyzed. Furthermore, a total of 188 primary triple negative breast cancer patients were enrolled in this study (diagnosed since January 2009 to January 2013 from the Second Hospital of Dalian Medical University). The protein levels of CCR7 were examined by immunohistochemistry using paraffin-embedded tumor tissues. Results: The analysis of gene amplification and mRNA levels showed the expression of CCR7 in breast cancer correlated with better prognosis. When we compared the CCR7 expressions in different subtypes, the basal-like group showed the highest expression of CCR7 and exhibited a better prognosis. Consistently, Kaplan–Meier analysis of 188 triple negative breast cancer patients showed that the prognosis of patients with positive CCR7 expression was significantly better than those with negative expression (HR=0.642, p=0.0275). Additionally, we also observed a positive correlation between lymph node metastasis and the CCR7 expression (p=0.0096). Conclusions: Our results indicated that elevated CCR7 expression as a marker for increased lymph node metastasis, in addition to serve as an independent prognostic indicator for better overall survival in triple negative breast cancer patients.

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“…The OS-RC-2 and 786-O cells were seeded on a 6-well plate and incubated with 50 nM siPGRMC1 or siNC per well. On the first day after siPGRMC1 treatment for RCC cells, cells were transfected with 2.5 µg pYR-ATP1A1 plasmids to further observe cell growth (31).…”

Section: Methodsmentioning

confidence: 99%

Combined assessment of low PGRMC1/positive ATP1A1 levels has enhanced prognostic value for renal cell carcinoma

Zhang

et al. 2018

Oncol Rep

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Progesterone receptor membrane component 1 (PGRMC1) and Na+/K+‑ATPase α1 subunit (ATP1A1) are two proteins associated with the clinical prognosis of renal cell carcinoma (RCC) and RCC cell proliferation. However, the two proteins have been previously studied independently, and their combined influence on the clinical outcome of RCC remains unclear. The present study suggests that the combined expression levels of PGRMC1 and ATP1A1 (PGRMC1/ATP1A1) are associated with the clinical prognosis of RCC patients. RCC patients with low PGRMC1/positive ATP1A1 levels exhibited the best overall survival (OS) outcomes (103.08±1.85 months). The high PGRMC1/negative ATP1A1 group demonstrated the worst prognosis (73.1±8.87 months). The low PGRMC1/positive ATP1A1 group had the highest 7‑year OS rate (92.3%). The high PGRMC1/negative ATP1A1 group had the lowest 7‑year OS rate (46.7%). Although PGRMC1 and ATP1A1 both act on AKT phosphorylation in RCC cells, their expression levels are independent of each other. Moreover, the synergistic suppressive roles of PGRMC1 downregulation combined with ATP1A1 upregulation exhibit more efficient tumor inhibition potentials on RCC cells. Therefore, combined assessment of the two biomarkers (PGRMC1/ATP1A1) shows enhanced prognostic ability for RCC.

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Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model

Cited by 15 publications

References 29 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

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer

Combined assessment of low PGRMC1/positive ATP1A1 levels has enhanced prognostic value for renal cell carcinoma

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