Rapamycin Combined with Immature Dendritic Cells Attenuates Obliterative Bronchiolitis in Trachea Allograft Rats by Regulating the Balance of Regulatory and Effector T Cells
Abstract:Background: Obliterative bronchiolitis (OB) ranks as the major obstacle for long-term survival of lung transplantation patients. Rapamycin (Rapa) has recently been confirmed as an immunosuppressant for antirejection due to its suppressive role in T cell activation. Here, we explore the effect of Rapa combined with immature dendritic cells (imDCs) on OB in trachea allograft rats. Methods: The effect of bone marrow-derived imDCs or Rapa-imDCs on lymphocyte cells and CD4+ T cells were evaluated by meth… Show more
“…In our preliminary study in which transplantation was performed between Brown Norway and LEW rats, the infusion of BMSCs promoted graft rejection, and it was also reported by other researchers that BMSCs promoted rejection between ACI and LEW rats (Inoue et al, ),—as such, we used the combination of WIS and LEW rats for the transplantation model. Some authors used this combination to investigate the in vivo transplantation model, and also in our study the untreated control group showed acute graft rejection with this combination (Dong, Wang, Liu, Zhao, Chen, Li, & Li, ). Third, we did not analyze the other immunological effects of recipient BMSCs, such as their homing effects, the induction of T cell regulation, and the modulation of dendritic cell maturation.…”
BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient immunosuppression.
“…In our preliminary study in which transplantation was performed between Brown Norway and LEW rats, the infusion of BMSCs promoted graft rejection, and it was also reported by other researchers that BMSCs promoted rejection between ACI and LEW rats (Inoue et al, ),—as such, we used the combination of WIS and LEW rats for the transplantation model. Some authors used this combination to investigate the in vivo transplantation model, and also in our study the untreated control group showed acute graft rejection with this combination (Dong, Wang, Liu, Zhao, Chen, Li, & Li, ). Third, we did not analyze the other immunological effects of recipient BMSCs, such as their homing effects, the induction of T cell regulation, and the modulation of dendritic cell maturation.…”
BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient immunosuppression.
“…This either points to special features of the sensitizing allergens, which become imprinted onto the involved dendritic cells, as discussed and entertained by the authors, or rather mirrors already elevated allergen-specific T effector cell levels present in such specifically sensitized individuals. These findings, together with the observation of Dong et al [57] that rapamycin-treated immature dendritic cells lead to the induction of Treg cells, add additional support to the concept that dendritic cells critically shape the T cellular immune response. Antigen-presenting cells receive important cues, such as ‘danger signals', by specifically sensing their environment with their specific set of surface receptors, including histamine receptors [58].…”
This review highlights the recent key advances in the biology of CD4+ effector T cells, antigen-presenting cells, Th17 and T regulatory cells, as well as immediate effector cells, such as mast cells, basophils and eosinophils, which are critically contributing to the better understanding of the pathophysiology of allergic diseases and are helping to improve their diagnosis and therapy. Some of the key advances with a direct impact on allergic asthma research and treatment are summarized.
“…Previous studies have shown that rapamycin, a typical mTOR inhibitor, inhibits T cell proliferation by preventing them from entering proliferative cell cycle . It has been generally accepted that rapamycin promotes CD4 + Foxp3 + T reg development . Here we demonstrated that kaempferol suppressed the proliferation of T cells and also dampened their mTOR signaling.…”
Psoriasis is an immune-mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti-inflammatory, anti-oxidant and anti-cancerous properties. However, it is unknown whether kaempferol is also anti-psoriatic. Here we established an imiquimod (IMQ)-induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis-like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3 + T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)-6, IL-17A and tumor necrosis factor (TNF)-α, in the psoriatic skin lesion. It also down-regulated proinflammatory nuclear factor kappa B (NF-κB) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4 + forkhead box protein 3 (FoxP3) + regulatory T cell (T reg ) frequency in the spleen and lymph nodes as well as FoxP3-positive staining in the skin lesion. Conversely, depletion of CD4 + CD25 + T regs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL-17A + CD4 + T cells in the spleen and lymph nodes of IMQ-induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.
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