Mechanisms by which chronic ethanol feeding limits the ability of dendritic cells to stimulate T-cell proliferation.
Mechanisms by which chronic ethanol feeding limits the ability of dendritic cells to stimulate T-cell proliferation.
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DOI：
10.1111/j.1530-0277.2010.01321.x
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Schlueter AJ
中科院分区：
文献类型：
--
作者：
Fan J;Edsen-Moore MR;Turner LE;Cook RT;Legge KL;Waldschmidt TJ;Schlueter AJ
树突状细胞（Dendritic cells，DC）作为免疫应答的启动者，在抗原特异性激活幼稚T细胞（naive T cells，naive T cells）以防御感染性病原体的过程中发挥重要作用。慢性酒精中毒者对感染的易感性和严重程度增加可能是由于幼稚T细胞应答的DC启动受损。具体而言，这些DC可能无法向这些T细胞提供足够的信号1（Ag呈递）、2（共刺激）或3（细胞因子产生）。使用慢性酒精滥用的Meadows-Cook小鼠模型，评估乙醇（EtOH）暴露的DC刺激T细胞增殖、获得和处理Ag、表达共刺激分子和产生炎性细胞因子的能力。与水喂养的对照小鼠相比，由EtOH暴露的DC引发的正常幼稚T细胞在体外和体内显示出降低的增殖。这些暴露于EtOH的DC在被CpG或TNFα激活后，上调共刺激分子CD 40、CD 80或CD 86的能力较低，产生的IL-12 p40、TNFα和IFNα也低于来自水喂养小鼠的DC。TLR 9和TNF受体的表达也减少/EtOH暴露的DC。未发现由于EtOH进料导致Ag采集或处理缺陷的证据。EtOH暴露的DC刺激后正常T细胞增殖不足可能是信号2和信号3减弱的结果。由于炎症介质受体减少，EtOH暴露的DC缺乏足够的炎症刺激似乎至少部分导致其功能障碍。这些发现提供了一种机制来解释酗酒者感染性疾病的发病率和死亡率增加，并提出了治疗干预的目标。
As initiators of immune responses, dendritic cells (DCs) are required for antigen (Ag) specific activation of naïve T cells in the defense against infectious agents. The increased susceptibility to and severity of infection seen in chronic alcoholics could be due to impaired DC initiation of naïve T cell responses. Specifically, these DC may not provide adequate Signals 1 (Ag presentation), 2 (costimulation), or 3 (cytokine production) to these T cells. Using the Meadows-Cook murine model of chronic alcohol abuse, the ability of ethanol (EtOH)-exposed DC to stimulate T cell proliferation, acquire and process Ag, express costimulatory molecules, and produce inflammatory cytokines was assessed. Normal naïve T cells primed by EtOH-exposed DCs showed decreased proliferation in vitro and in vivo, compared to water-fed control mice. These EtOH-exposed DC, after activation by CpG or TNFα, were less able to upregulate costimulatory molecules CD40, CD80, or CD86, and produced less IL-12 p40, TNFα and IFNα than DC from water-fed mice. TLR9 and TNF receptor expression were also reduced in/on EtOH-exposed DC. No evidence of defective Ag acquisition or processing as a result of EtOH feeding was identified. Inadequate proliferation of normal T cells following stimulation by EtOH-exposed DC is likely a result of diminished Signal 2 and Signal 3. Lack of adequate inflammatory stimulation of EtOH-exposed DC due to diminished receptors for inflammatory mediators appears to be at least partially responsible for their dysfunction. These findings provide a mechanism to explain increased morbidity and mortality from infectious diseases in alcoholics, and suggest targets for therapeutic intervention.
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DOI：
10.1084/jem.20021910
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Curtsinger JM;Lins DC;Mescher MF
通讯作者：
Mescher MF
DOI：
10.1084/jem.178.6.2185
发表时间：
1993-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Freeman GJ;Borriello F;Hodes RJ;Reiser H;Gribben JG;Ng JW;Kim J;Goldberg JM;Hathcock K;Laszlo G
通讯作者：
Laszlo G
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
3.3
作者：
Chang, MP;Norman, DC
通讯作者：
Norman, DC
DOI：
10.1111/j.1530-0277.2008.00699.x
发表时间：
2008-07-01
影响因子：
3.2
作者：
Edsen-Moore, Michelle R.;Fan, Ji;Schlueter, Annette J.
通讯作者：
Schlueter, Annette J.