人间充质干细胞调节同种异源免疫细胞应答

deron

主题：人间充质干细胞调节同种异源免疫细胞应答' C9 D) B# W& E
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说明：原文来自Blood，干细胞之家新闻小组成员deron翻译（转帖请注明）: t: f+ N: [) \6 C
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间充质干细胞（MSCs）是在一些成体组织中发现的多能细胞。扩展时标显示受体中能够检测到移植的同种异源MSCs，这表明受体（对MSCs）缺乏免疫识别和免疫清除。最近也有报道骨髓来源MSCs在同种异源移植中可以降低移植物抗宿主疾病（GVHD）的发病率和严重性；但其作用机制仍有待研究。通过与纯化免疫细胞亚群共培养的方式，我们研究了人MSCs（hMSCs）的免疫调节功能，本文报道了人MSC将树突状细胞（DCs）、幼稚和效应T细胞（T辅助1[TH1]和TH2）以及自然杀伤（NK）细胞的细胞因子分泌表型转化成为诱导更具抗炎性或耐受的表型。具体来说，hMSCs诱导成熟DCs1型细胞（DC1）降低肿瘤坏死因子α（TNF-α）表达，诱导成熟DC2上调白介素10（IL10）的表达；hMSCs诱导TH1细胞下调干扰素γ（IFNγ）表达并诱导TH2细胞上调IL4的表达；hMSCs上调现有调节性T细胞（TRegs）比例；并下调了NK细胞IFNγ的分泌。理论上讲，hMSCs在共培养中上调前列腺素E2（PGE2）的表达，并且PGE2合成过程的抑制剂减缓了hMSC介导的免疫调节。这些数据有助于（研究者）深入理解同种异源MSCs和免疫细胞的相互作用，并为可能涉及体内MSC介导耐受的诱导提供了分子机理，以应用于降低GVHD、排斥和调节炎症的治疗。
* t1 r( a: ]1 E3 S+ ^8 x原摘要：Mesenchymal stem cells (MSCs) are multipotent cells found in several adult tissues. Transplanted allogeneic MSCs can be detected in recipients at extended time points, indicating a lack of immune recognition and clearance. As well, a role for bone marrow-derived MSCs in reducing the incidence and severity of graft-versus-host disease (GVHD) during allogeneic transplantation has recently been reported; however, the mechanisms remain to be investigated. We examined the immunomodulatory functions of human MSCs (hMSCs) by coculturing them with purified subpopulations of immune cells and report here that hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (T helper 1 [T(H)1] and T(H)2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature DCs type 1 (DC1) to decrease tumor necrosis factor alpha (TNF-alpha) secretion and mature DC2 to increase interleukin-10 (IL-10) secretion; hMSCs caused T(H)1 cells to decrease interferon gamma (IFN-gamma) and caused the T(H)2 cells to increase secretion of IL-4; hMSCs caused an increase in the proportion of regulatory T cells (T(Regs)) present; and hMSCs decreased secretion of IFN-gamma from the NK cells. Mechanistically, the hMSCs produced elevated prostaglandin E2 (PGE(2)) in co-cultures, and inhibitors of PGE(2) production mitigated hMSC-mediated immune modulation. These data offer insight into the interactions between allogeneic MSCs and immune cells and provide mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation.# h6 n4 D7 @: |4 u3 T  X

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补充：一张好图
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deron

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naturalkillerce

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“Transplanted allogeneic MSCs can be detected in recipients at extended time points”可尝试翻译为“在延伸的时间点上，能够在受体内检测到移植的同种异源MSC”

naturalkillerce

by coculturing them with purified subpopulations of immune cells，即通过将人MSC与纯化的免疫细胞亚群共培养。$ j( [5 I! W% N, f

0 D0 g1 u- U  s9 J hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (T helper 1 [T(H)1] and T(H)2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype.即hMSCs改变了树突状细胞、初始T细胞(naive T cells)、效应T细胞和自然杀伤细胞的细胞因子分泌谱，从而诱导产生一个更加抗炎性或耐受性的表型。

李小崽

求全文英文名称啊~~