IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells.
IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells.
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DOI：
10.1016/j.imlet.2012.03.006
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发表时间：
2012-05-30
影响因子：
4.4
通讯作者：
Kao, John Y.
中科院分区：
文献类型：
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作者：
Cole, Tyler S.;Zhang, Min;Standiford, Theodore J.;Newstead, Michael;Luther, Jay;Zhang, Jiajie;Chen, Chun-Chia;Kao, John Y.
关键词：
树突状细胞（dendritic cells，DCs）是先天免疫系统的重要组成部分，能直接与病原体相互作用并参与获得性免疫应答。在与DC密切相关的细胞中，如巨噬细胞和单核细胞，先前暴露于微量内毒素可导致不应期，随后暴露于更高剂量不能诱导炎症反应;很少有研究调查这种对DC的影响。本研究测试了小鼠骨髓来源的树突状细胞（BM-DCs）是否通过降低炎症反应和增加抗炎反应来响应内毒素和细菌超声处理诱导的耐受性，以及IRAK-M（TLR信号传导的细胞内负调节剂）在这种耐受性中的作用。与未耐受的细胞相比，耐受的BM-DCs表现出TNF-α和IL-12 p70产生的显著下降以及IL-10表达的增加。BM-DCs还显示出产生异源耐受的能力，其中单独的LPS暴露能够诱导对幽门螺杆菌超声处理和TLR 2激动剂Pam 3Cys的耐受。此外，如qPCR和Western印迹所确定的，在再刺激耐受化的BM-DCs后IRAK-M的表达增加。IRAK-M对LPS耐受的BM-DCs中主要组织相容性复合物II类（MHC II）和CD 80的表面表达具有抑制作用。与野生型BM-DC相比，细菌超声处理耐受化的IRAK-M−/− BM-DC中的IL-10表达改变，耐受化的IRAK-M−/− BM-DC中耐受诱导的IL-10表达减轻。沿着内毒素，细菌超声处理能够诱导BM-DCs中的难治性耐受，并且IRAK-M在调节该耐受期间的MHC II类和CD 80的细胞表面表达以及IL-10的释放中起作用。
As essential components of the innate immune system, dendritic cells (DCs) can interact directly with pathogens as well as participate in the adaptive immune response. In cells closely related to DCs such as macrophages and monocytes, prior exposure to minute amounts of endotoxin can lead to a refractory period where subsequent exposure to higher doses fails to induce an inflammatory response; little research has investigated this effect on DCs. This study tested if murine bone marrow-derived dendritic cells (BM-DCs) respond to endotoxin- and bacterial sonicate-induced tolerance by decreased inflammatory and increased anti-inflammatory response, and the role of IRAK-M, an intracellular negative regulator of TLR signaling, in this tolerance. Tolerized BM-DCs exhibited a significant drop in TNF-α and IL-12p70 production and increased IL-10 expression compared to untolerized cells. BM-DCs also showed the ability to develop heterotolerance, in which the LPS exposure alone was able to induce tolerance to Helicobacter pylori sonicate and TLR2 agonist Pam3Cys. Furthermore, the expression of IRAK-M was increased after restimulation of tolerized BM-DCs as determined qPCR and Western blot. IRAK-M exhibited a suppressive effect on surface expression of major histocompatibilty complex class II (MHC II) and CD80 in LPS-tolerized BM-DCs. IL-10 expression in bacterial sonicate-tolerized IRAK-M−/− BM-DCs was altered as compared to wild type BM-DCs, with tolerance-induced expression of IL-10 mitigated in tolerized IRAK-M−/− BM-DCs. Along with endotoxin, bacterial sonicate is able to induce refractory tolerance in BM-DCs, and IRAK-M plays a role in modulating cell surface expression of MHC class II and CD80 and release of IL-10 during this tolerance.
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DOI：
10.1016/j.biocel.2007.04.021
发表时间：
2007-01-01
影响因子：
4
作者：
Biswas, Subhra K.;Tergaonkarl, Vinay
通讯作者：
Tergaonkarl, Vinay
DOI：
10.1177/0968051907078623
发表时间：
2007-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
del Fresno, Carlos;Soler-Rangel, Llanos;Lopez-Collazo, Eduardo
通讯作者：
Lopez-Collazo, Eduardo
影响因子：
4.3
作者：
Hassan, Ferdaus;Islam, Shamima;Yokochi, Takashi
通讯作者：
Yokochi, Takashi
影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan
影响因子：
82.9
作者：
通讯作者：
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