In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells （toI-DCs） with immunoregulatory functions have attracted...In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells （toI-DCs） with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various toI-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.展开更多
Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,s...Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.展开更多
Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract for which no curative treatment is available. Research in other fields with stem cells of different sources and wi...Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract for which no curative treatment is available. Research in other fields with stem cells of different sources and with immunoregulatory cells(regulatory T-lymphocytes and dendritic T-cells) opens up new expectations for their use in these diseases. The goal for stem cell-based therapy is to provide a permanent cure. To achieve this, it will be necessary to obtain a cellular product, original or genetically modified, that has a high migration capacity and homes into the intestine, has high survival after transplantation, regulates the immune reaction while not being visible to the patient's immune system, and repairs the injured tissue.展开更多
文摘In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells （toI-DCs） with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various toI-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.
基金supported by the National Key R&D Program of China(No.2020YFA0908004)the National Natural Science Foundation of China(Nos.82293684,82293680,82273936,82273929)+1 种基金CAMS Innovation Fund for Medical Science(No.2021-I2M-1-028,2022-I2M-2-002,2022-I2M-1-014,China)Natural Science Fund for Distinguished Young Scholars of Tianjin(No.21JCJQJC00020,China)。
文摘Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.
文摘Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract for which no curative treatment is available. Research in other fields with stem cells of different sources and with immunoregulatory cells(regulatory T-lymphocytes and dendritic T-cells) opens up new expectations for their use in these diseases. The goal for stem cell-based therapy is to provide a permanent cure. To achieve this, it will be necessary to obtain a cellular product, original or genetically modified, that has a high migration capacity and homes into the intestine, has high survival after transplantation, regulates the immune reaction while not being visible to the patient's immune system, and repairs the injured tissue.
文摘大量研究证实,肿瘤患者体内存在广泛的免疫逃逸现象。目前所知肿瘤逃逸的机制很多,其中重要的一个就是树突状细胞( Dendritic cell,DC )的分化成熟异常导致的功能障碍DC是目前已知的体内最重要的抗原递呈细胞,在不同发育阶段有不同的亚型、表达不同的分子并有不同的生物学行为。传统认为,DC分化的不成熟发育阶段能够诱导T细胞无能或调节性T细胞(Regulatory T cel l,Treg)生成,经过活化刺激后则转化成为成熟DC,则认为其具有了免疫原性并能触发初级T细胞反应。但是,近年来研究显示,某些半成熟或成熟表型的DC也能诱导耐受发生,其诱导耐受的机制是通过分泌IL-10、TGF-β等细胞因子而发挥作用的本文就能够诱导Treg或无反应T细胞的这群耐受型DC(Tolerogenic dendritic cell,TDC)
