间充质干细胞通过一种白介素6依赖机制抑制树突状细胞的分化

deron

主题：间充质干细胞通过一种白介素6依赖机制抑制树突状细胞的分化' k, V- [( C* F, q' k

% f" y( d* n$ u" W! d' z说明：原文来自Stem Cell，干细胞之家新闻小组成员deron翻译（转帖请注明）
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间充质干细胞（MSC）除了能够降低同种异源移植中移植物抗宿主病发病率和发病程度外，其在组织工程学中的潜在临床应用前景也同样引人注目。之前我们已经证明间充质干细胞通过刺激诱导可溶性分子的分泌来发挥免疫抑制作用。本研究的目的在于识别涉及其中的分子以及潜在的分子机制。我们证明了鼠MSC分泌高水平的白介素（IL）6和血管内皮生长因子，二者与抑制T细胞增殖直接相关。在加入中和性的抗IL6抗体或者前列腺素E2抑制剂吲哚美辛后，T细胞活化部分恢复。有趣的是，在我们的培养基中未检测到吲哚胺2，3加双氧酶的活性。取而代之的是，我们证明了MSC降低了成熟树突状细胞（DC）表面主要组织相容性抗原Ⅱ类分子、CD40和CD86共刺激分子的表达，这种下调导致了T细胞增殖水平的下降。更重要的是，我们证明了：用MSC来源条件上清培养的骨髓祖细胞向DC细胞的分化被（MSC）分泌的IL6部分抑制。总而言之，这些数据表明IL6通过部分抑制DC分化参与MSC介导的免疫调节机制，但这可能不是主导机制。& d' Y. g+ r! G$ i
原摘要：Mesenchymal stem cells (MSC) are of particular interest for their potential clinical use in tissue engineering as well as for their capacity to reduce the incidence and severity of graft-versus-host disease in allogeneic transplantation. We have previously shown that MSC-mediated immune suppression acts via the secretion of soluble factor(s) induced upon stimulation. The aim of this study was to identify the molecule(s) involved and the underlying mechanism(s). We show that murine MSC secrete high levels of interleukin (IL)-6 and vascular endothelial growth factor, which are directly correlated to the inhibition of T-cell proliferation. The T-cell activation is partially restored upon addition of a neutralizing anti-IL-6 antibody or the prostaglandin E2 inhibitor indomethacin. Interestingly, no indoleamine 2,3-dioxygenase activity was detected in our conditions. Instead, we show that MSC reduce the expression of major histocompatibility complex class II, CD40, and CD86 costimulatory molecules on mature dendritic cells (DC), which was responsible for a decrease in T-cell proliferation. Moreover, we show that the differentiation of bone marrow progenitors into DC cultured with conditioned supernatants from MSC was partly inhibited through the secretion of IL-6. Altogether, these data suggest that IL-6 is involved in the immunoregulatory mechanism mediated by MSC through a partial inhibition of DC differentiation but is probably not the main mechanism. Disclosure of potential conflicts of interest is found at the end of this article.+ v+ T: r# w: v& j

8 g5 w; d2 m1 w& A' X% U$ [原文：

naturalkillerce

回复 deron 的帖子2 u" A& L0 L% X" r! n! H; e: e

; M6 m9 [, Z2 K5 D呵呵。又来参与了。% Q' ]$ V( a' W2 G9 G. b2 w
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underlying mechanism(其背后的分子机制：虽然也有潜在性的意思，但是一套机制是有的，所以不应是潜在的，若表达潜在的意思，多用potential。), y) R2 u* J, u) D2 Z6 @

0 U% R, E* c( U) d% o8 o4 E$ Y3 e9 Qseverity(最好是严重性，而不是楼主的“发病程度”，更能贴合原文)8 K0 f0 F  l4 l

, w6 P3 i- g8 n. r7 K& v3 b& C in our conditions(最好翻译为“在我们的实验条件下”，而不是“在我们的培养基中”，因为培养基只是其中一个条件)% X. K; a% H" }# [* Z
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major histocompatibility complex class II应是主要组织相容性复合体II类分子，而不是楼主的“主要组织相容性抗原Ⅱ类分子”1 x$ j& H) F. @8 q

/ c9 C( `6 H  a- K$ ~- Pwe show that the differentiation of bone marrow progenitors into DC cultured with conditioned supernatants from MSC was partly inhibited through the secretion of IL-6。
# u. P- {; }3 T' V) Y7 S: U$ @( b试译：我们证实在来自间充质干细胞的培养上清液培养时，骨髓祖细胞分化为树突状细胞部分受到(间充质干细胞分泌的)IL-6的抑制。

deron

回复 naturalkillerce 的帖子" r$ @9 ?" q4 t! o; U
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都是自己忽略的东西，承蒙指教

haoyan222

间充质干细胞是未来细胞移植和治疗领域的一个潜力股，拥有广阔的前景