Enhanced activation of dendritic cells by autologous apoptotic microvesicles in MRL/lpr mice.
Enhanced activation of dendritic cells by autologous apoptotic microvesicles in MRL/lpr mice.
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DOI：
10.1186/s13075-015-0617-2
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发表时间：
2015-04-16
影响因子：
4.9
通讯作者：
van der Vlag J
中科院分区：
文献类型：
--
作者：
Dieker J;Hilbrands L;Thielen A;Dijkman H;Berden JH;van der Vlag J
系统性红斑狼疮与修饰的含有自身抗原的凋亡碎片的持续循环有关，这种碎片可能能够打破耐受性。我们的目的是评估从狼疮或对照小鼠获得的凋亡微囊是否存在与凋亡相关的染色质修饰，以及它们刺激狼疮和对照小鼠树突状细胞(DC)的能力。体外从MRL/LPR狼疮小鼠和正常BALB/c小鼠的脾细胞和血浆中分离到凋亡微囊。用流式细胞仪分析微囊泡。将培养自MRL/LPR或BALB/c小鼠的骨髓来源的DC与微囊共同孵育，检测CD40表达和细胞因子的产生。与BALB/c小鼠相比，MRL/LPR小鼠的凋亡脾细胞或血浆来源的微囊含有更多的修饰染色质，并且显示出增强了来自MRL/LPR或BALB/c小鼠的DC的激活，并连续增强了DC介导的脾细胞的激活。凋亡脾细胞微泡中凋亡修饰染色质的含量与其诱导DC产生IL-6的能力相关。与BALB/c DC相比，微囊激活的mRL/LPR DC产生的IL-6和肿瘤生长因子-β(TGFR-β)显著增加，并且对脾细胞的激活作用更强。来自MRL/LPR小鼠的凋亡微泡是DC更有效的激活剂，而来自MRL/LPR小鼠的DC对凋亡微泡的激活相对更敏感。我们的研究结果表明，在MRL/LPR小鼠中，凋亡微泡和DC水平的异常有助于对染色质的自身免疫反应。
Systemic lupus erythematosus is associated with a persistent circulation of modified autoantigen-containing apoptotic debris that might be capable of breaking tolerance. We aimed to evaluate apoptotic microvesicles obtained from lupus or control mice for the presence of apoptosis-associated chromatin modifications and for their capacity to stimulate dendritic cells (DC) from lupus and control mice. Apoptotic microvesicles were in vitro generated from splenocytes, and ex vivo isolated from plasma of both MRL/lpr lupus mice and normal BALB/c mice. Microvesicles were analyzed using flow cytometry. Bone marrow-derived (BM)-DC cultured from MRL/lpr or BALB/c mice were incubated with microvesicles and CD40 expression and cytokine production were determined as measure of activation. Microvesicles derived from apoptotic splenocytes or plasma of MRL/lpr mice contained more modified chromatin compared to microvesicles of BALB/c mice, and showed enhanced activation of DC, either from MRL/lpr or BALB/c mice, and consecutively an enhanced DC-mediated activation of splenocytes. The content of apoptosis-modified chromatin in microvesicles of apoptotic splenocytes correlated with their potency to induce interleukin-6 (IL-6) production by DC. Microvesicle-activated MRL/lpr DC showed a significant higher production of IL-6 and tumor growth factor-β (TGF-β) compared to BALB/c DC, and were more potent in the activation of splenocytes. Apoptotic microvesicles from MRL/lpr mice are more potent activators of DC, and DC from MRL/lpr mice appear relatively more sensitive to activation by apoptotic microvesicles. Our findings indicate that aberrations at the level of apoptotic microvesicles and possibly DC contribute to the autoimmune response against chromatin in MRL/lpr mice.
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影响因子：
4.9
作者：
Fransen JH;van der Vlag J;Ruben J;Adema GJ;Berden JH;Hilbrands LB
通讯作者：
Hilbrands LB
影响因子：
3.5
作者：
Fransen, J. H.;Hilbrands, L. B.;Van Der Vlag, J.
通讯作者：
Van Der Vlag, J.
影响因子：
2.6
作者：
Munoz, L. E.;van Bavel, C.;van der Vlag, J.
通讯作者：
van der Vlag, J.
DOI：
10.1073/pnas.0705268104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Kimura, Akihiro;Naka, Tetsuji;Kishimoto, Tadamitsu
通讯作者：
Kishimoto, Tadamitsu
影响因子：
56.9
作者：
Matzinger, P
通讯作者：
Matzinger, P