Mechanisms by which chronic ethanol feeding impairs the migratory capacity of cutaneous dendritic cells.
Mechanisms by which chronic ethanol feeding impairs the migratory capacity of cutaneous dendritic cells.
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DOI：
10.1111/acer.12201
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Schlueter AJ
中科院分区：
文献类型：
--
作者：
Parlet CP;Schlueter AJ
慢性酒精中毒与皮肤感染的发病率和严重程度增加有关。皮肤树突状细胞（CDC）在皮肤免疫中起关键作用，并且已显示小鼠中的慢性乙醇（EtOH）喂养抑制CDC在表皮致敏后迁移至皮肤引流淋巴结（dLN）。由于CDC亚群差异启动T细胞反应，重要的是要确定EtOH喂养如何影响每个亚群的迁移，并确定机制负责观察到的缺陷。小鼠在饮用水中接受EtOH ≥16周。通过流式细胞术评估CDC亚群的基线数量及其在FITC致敏后向dLN的迁移。表皮细胞悬浮液和皮肤外植体培养物用于测量EtOH对影响CDC迁移的分子的影响。在外植体培养上清液上进行的细胞因子阵列评估炎性细胞因子的局部产生。慢性EtOH喂养减少了FITC致敏后所有CDC亚群向dLN的迁移。减少迁移的真皮驻留CDC并不对应于这些细胞的基线数量减少。对于朗格汉斯细胞（LC），乙醇诱导的迁移功能障碍对应于延迟下调E-钙粘蛋白，CCR 1和CCR 6和受损的上调基质金属蛋白酶（MMPs）2和9。在皮肤外植体测定中，在用CCL 21/CPG 1826刺激后，EtOH减弱CDC动员。未观察到CD 54或CCR 7表达的改变，但皮肤源性TNFα的产生减少。通过向EtOH喂养小鼠的外植体培养物中补充TNFα，可改善体外迁移反应不良。慢性EtOH消耗不会改变基线皮肤居民CDC数字。然而，像LC一样，皮肤CDCs的迁移反应性在FITC致敏后降低。CCRs和粘附分子的低效下调和不能上调MMP表明EtOH阻碍LC获得促迁移表型。这些缺陷与体外TNFα替代对迁移缺陷的改善相结合，证明了对缺陷性CDC迁移的内在和环境贡献。这些发现提供了新的机制来解释观察到的慢性酗酒者皮肤感染的发病率和严重程度增加。
Chronic alcoholism is associated with increased incidence and severity of skin infection. Cutaneous dendritic cells (CDCs) play a pivotal role in skin immunity, and chronic ethanol (EtOH) feeding in mice has been shown to inhibit CDC migration to skin-draining lymph nodes (dLNs) following epicutaneous sensitization. Since CDC subsets differentially initiate T cell responses, it is important to determine how EtOH feeding affects migration of each subset and identify mechanisms responsible for observed defects. Mice received EtOH in the drinking water for ≥16 weeks. Baseline numbers of CDC subsets and their migration to the dLNs following FITC sensitization were assessed by flow cytometry. Epidermal cell suspension and skin explant cultures were used to measure the impact of EtOH upon molecules that influence CDC migration. Cytokine arrays performed on explant culture supernatants assessed local production of inflammatory cytokines. Chronic EtOH feeding reduced migration of all CDC subsets to the dLNs following FITC sensitization. Reduced migration of dermal-resident CDCs did not correspond with reduced baseline numbers of these cells. For Langerhans cells (LCs), EtOH-induced migratory dysfunction corresponded with delayed down-regulation of E-cadherin, CCR1 and CCR6 and impaired upregulation of matrix metalloproteinases (MMPs) 2 and 9. In skin explant assays, EtOH blunted CDC mobilization following stimulation with CCL21/CPG 1826. No alteration in CD54 or CCR7 expression was observed, but production of skin-derived TNFα was reduced. Poor migratory responses in vitro could be improved by supplementing explant cultures from EtOH-fed mice with TNFα. Chronic EtOH consumption does not alter baseline dermal-resident CDC numbers. However, like LCs, migratory responsiveness of dermal CDCs was decreased following FITC sensitization. Inefficient downregulation of both CCRs and adhesion molecules and the inability to upregulate MMPs indicates that EtOH impedes LC acquisition of a promigratory phenotype. These defects, combined with improvement of the migratory defect with in vitro TNFα replacement, demonstrate intrinsic as well as environmental contributions to defective CDC migration. These findings provide novel mechanisms to explain the observed increased incidence and severity of skin infections in chronic alcoholics.
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DOI：
10.1084/jem.20071966
发表时间：
2007-12-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bursch LS;Wang L;Igyarto B;Kissenpfennig A;Malissen B;Kaplan DH;Hogquist KA
通讯作者：
Hogquist KA
影响因子：
4.4
作者：
Mandrekar, P;Catalano, D;Szabo, G
通讯作者：
Szabo, G
DOI：
10.1084/jem.20030448
发表时间：
2003-08-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
MartIn-Fontecha A;Sebastiani S;Höpken UE;Uguccioni M;Lipp M;Lanzavecchia A;Sallusto F
通讯作者：
Sallusto F
影响因子：
30.5
作者：
Bedoui, Sammy;Whitney, Paul G.;Heath, William R.
通讯作者：
Heath, William R.
影响因子：
4.4
作者：
Meyerholz, David K.;Edsen-Moore, Michelle;Legge, Kevin L.
通讯作者：
Legge, Kevin L.