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首页> 外文期刊>Aging cell. >Donor BMSC-derived small extracellular vesicles relieve acute rejection post-renal allograft through transmitting Loc108349490 to dendritic cells
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Donor BMSC-derived small extracellular vesicles relieve acute rejection post-renal allograft through transmitting Loc108349490 to dendritic cells

机译：供体BMSC衍生的小细胞外囊囊泡通过将LOC108349490传递给树突细胞来缓解急性排斥反射后肾脏异种移植物

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Bone marrow-derived mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are potent candidates for the suppression of acute rejection post-renal allograft and have been reported to halt dendritic cells (DCs) maturation. However, whether BMSC-derived sEVs mitigate acute rejection post-renal allograft by targeting DCs is still unclear. In this study, donor BMSC-derived sEVs (sEVs) relieved the inflammatory response and suppressed mature DCs (mDCs) location in kidney grafts, and increased regulatory T (Treg) cell population in the spleens of the rats that underwent kidney allograft. In lipopolysaccharide (LPS)-stimulated immature DCs (imDCs), sEVs suppressed the maturation and migration of DCs and inactivated toll-like receptor 4 (TLR4) signaling. Compared with LPS-treated imDCs, imDCs treated with LPS+sEVs promoted CD4 + T cells differentiated toward Treg cells. Subsequently, we found that Loc108349490, a long non-coding RNA (lncRNA) abundant in sEVs, mediated the inhibitory effect of sEVs on DC maturation and migration by promoting TLR4 ubiquitination. In rats that underwent an allograft, Loc108349490 deficiency weakened the therapeutic effect of sEVs on acute rejection. The present study firstly found that sEVs alleviated acute rejection post-renal allograft by transferring lncRNA to DCs and screened out the functional lncRNA loaded in sEVs was Loc108349490.
机译：骨髓衍生的间充质干细胞（BMSC）的小细胞外囊泡（SEVS）是抑制急性排斥肾后移植移植物的有效候选者，并据报道暂停树突细胞（DCS）成熟。然而，BMSC衍生的SED是否通过靶向DCS减轻急性排斥术后肾脏异种移植物仍不清楚。在该研究中，供体BMSC衍生的SEVS（SED）缓解了肾移植物中的炎症反应和抑制成熟的DC（MDCS）位置，以及在肾同种异体移植物的大鼠的脾脏中增加的调节性T（Treg）细胞群。在脂多糖（LPS） - 刺激的未成熟DCS（IMDC）中，SEVS抑制了DCS和灭活的Toll样受体4（TLR4）信号传导的成熟和迁移。与LPS处理的IMDC相比，用LPS + SEV处理的IMDC促进了与Treg细胞分化的CD4 + T细胞。随后，我们发现LOM108349490，SEVS中丰富的长编码RNA（LNCRNA），通过促进TLR4泛素介绍了SEVS对DC成熟和迁移的抑制作用。在接受同种异体移植物的大鼠中，LOM108349490缺乏削弱了SEVS对急性排斥反应的治疗效果。本研究首先发现，通过将LNCRNA转移到DC并筛选输出在SED中的功能性LNCRNA筛选的急性排斥急性排斥肾肾上腺移植物是LOM108349490。

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