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

2017 ◽  
Vol 42 (2) ◽  
pp. 455-468 ◽  
Author(s):  
Zhiwei Dong ◽  
Yajie Chen ◽  
Yuan Peng ◽  
Fan Wang ◽  
Zichen Yang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Graft Survival ◽  
Skin Graft ◽  
Immune Tolerance ◽  
Migration Rate ◽  
Recombinant Adenovirus ◽  
Treg Cells ◽  
Skin Transplantation ◽  
Immune Rejection ◽  
Immature Dendritic Cells

Background/Aims: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. Methods & Results: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection.

In vitro maturation and migration of immature dendritic cells after chemokine receptor 7 transfection

2009 ◽  
Vol 55 (7) ◽  
pp. 859-866 ◽  
Author(s):  
Hai-ming Xin ◽  
Yi-zhi Peng ◽  
Zhi-qiang Yuan ◽  
Hao Guo
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Chemokine Receptor ◽  
Recombinant Adenovirus ◽  
Gene Transfection ◽  
Interleukin 10 ◽  
Lymphoid Organs ◽  
Immature Dendritic Cells ◽  
Secondary Lymphoid Organs

Dendritic cells are specialized antigen-presenting cells that regulate immunity and tolerance. Chemokine receptor 7 (CCR7), which is expressed by mature dendritic cells, mediates the migration of the cells to secondary lymphoid organs and thus regulates immune responses. It has been demonstrated that immature dendritic cells can induce immune tolerance, but they do not express CCR7 and cannot migrate to secondary lymphoid organs. We transfected immature dendritic cells with a recombinant adenovirus carrying the CCR7 gene to obtain immature dendritic cells with the ability to migrate. The maturity of the cells was monitored by scanning electron microscopy and flow cytometry. In addition, we assessed the ability of cells to migrate and the function of the cells using in vitro chemotactic and mixed leukocyte reaction assays. The results showed that immature dendritic cells became semi-mature, exhibiting a mild upregulation of co-stimulatory molecular expression and a few dendritic processes. Immunofluorescence assay and Western blotting indicated that CCR7 protein expression increased significantly in immature dendritic cells following CCR7 gene transfection. The in vitro chemotactic assay showed a significantly enhanced ability to migrate in response to CCL19 following CCR7 gene transfection. Moreover, transfected cells showed an enhanced ability to stimulate allogeneic T cell proliferation in vitro, but their ability was significantly weaker than that of mature dendritic cells. Interleukin-10 inhibited the differentiation and maturation of immature dendritic cells. It is concluded that, following CCR7 gene transfection, immature dendritic cells exhibit an enhanced ability to migrate and some of the characteristics of mature cells. Thus, these cells are of potential clinical significance in studies of immune tolerance induction during skin grafting after severe burns.

scholarly journals Induced immune tolerance of autoantigen loaded immature dendritic cells in homogenic lupus mice

2014 ◽  
Vol 13 (1) ◽  
pp. 1251-1262 ◽  
Author(s):  
J. Xie ◽  
Y.K. Lin ◽  
K. Wang ◽  
B. Che ◽  
J.Q. Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Immature Dendritic Cells

scholarly journals Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Transplant Recipients ◽  
T Helper ◽  
T Helper 2 ◽  
Immature Dendritic Cells ◽  
And Migration ◽  
Mixed Lymphocyte Reactions ◽  
Dc Maturation

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.

Abstract 16582: Costimulation Blockade With Anti Cd80 and Cd86 Monoclonal Antibodies Prolonged Graft Survival in Allogeneic Ips Cell-Derived Cardiomyocyte Patch Transplantation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Masaro Nakae ◽  
Shigeru Miyagawa ◽  
Takuji Kawamura ◽  
Koichiro Uchida ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
Graft Survival ◽  
Immune Tolerance ◽  
Immune Rejection ◽  
Mice Model ◽  
Ips Cell ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
Costimulatory Pathway

Introduction: How to avoid immune rejection after transplantation should be elucidated for confirmed efficacy in clinical application of allogenic induced pluripotent stem cell derived cardiomyocyte patch. The blockade of CD28-CD80/86 costimulation is known to induce T cell anergy and immune tolerance by the recruitment of regulatory T cells (T reg) and prolong graft survival in organ transplantation. Hypothesis: We hypothesized that the blockade of CD28-CD80/CD86 costimulatory pathway by anti-CD80/CD86 monoclonal antibodies (mAbs) induces T cell anergy in vivo and suppresses immune rejection in allogeneic iPSC-CMs subcutaneous transplantation mice model. Methods: T cell anergy was induced in vitro by co-culture of Balb/c and 25Gy irradiated C57BL/6 splenocytes with anti-CD80/86 mAbs for 5 days. The inhibitory effect of anergic cells was evaluated by mixed lymphocyte reaction (MLR) in C57BL/6 and Balb/c splenocytes with anergic cells. IFN-g in MLR supernatants was measured by ELISAs to assess immune response. C57BL/6 iPSC-CMs expressing luciferase were subcutaneously transplanted into Balb/c. Anti-CD80/CD86 mAbs were injected intraperitoneally 250μg/dose on day 0, 1, and 2 (treated mice, n=6). In control mice (n=6), equivalent volume of saline was injected. To evaluate iPSC-CMs graft survival, photon counts of iPSC-CMs were measured by bioluminescence imaging system (BLI). Cells of harvested grafts were analyzed by immunofluorescence staining (IF). Results: On ELISAs, IFN-g in MLR supernatants co-cultured with anergic cells was significantly lower as compared with those without anergic cells (12.3±14.4 vs. 251±80.2 pg/ml, p=0.007). The ability to suppress the alloresponses was dose-dependent. BLI showed that photon counts on day 14 in treated mice were significantly higher than in control mice (7397±2651 vs. 2703±1271, p=0.003). IF showed a siginificantly higher ratio of CD4 and Foxp3 double positive cells to CD4-postive cells in the grafts on day 7 in treated mice as compared with in control mice (23±3% vs. 9±3%, p=0.009) Conclusions: The blockade of CD28-CD80/CD86 costimulatory pathway might suppress immune rejection in allogeneic iPSC-CMs transplantation mice model and T reg might involve this immune tolerance.

Dendritic cells expressing soluble CTLA4Ig prolong antigen‐specific skin graft survival

2010 ◽  
Vol 88 (8) ◽  
pp. 846-850 ◽  
Author(s):  
Francesco L Ierino ◽  
William Mulley ◽  
Natalie Dodge ◽  
Yu Qin Li ◽  
Effie Mouhtouris ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Graft Survival ◽  
Skin Graft

scholarly journals Immature dendritic cells derived exosomes promotes immune tolerance by regulating T cell differentiation in renal transplantation

Aging ◽  
2019 ◽  
Vol 11 (20) ◽  
pp. 8911-8924 ◽  
Author(s):  
Xin-Lu Pang ◽  
Zhi-Gang Wang ◽  
Lei Liu ◽  
Yong-Hua Feng ◽  
Jun-Xiang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Renal Transplantation ◽  
Cell Differentiation ◽  
T Cell ◽  
Immune Tolerance ◽  
T Cell Differentiation ◽  
Immature Dendritic Cells
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