Cigarette smoke differentially modulates dendritic cell maturation and function in time.
Cigarette smoke differentially modulates dendritic cell maturation and function in time.
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DOI：
10.1186/s12931-015-0291-6
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发表时间：
2015-10-24
影响因子：
5.8
通讯作者：
Mortaz E
中科院分区：
文献类型：
--
作者：
Givi ME;Folkerts G;Wagenaar GT;Redegeld FA;Mortaz E
树突状细胞（Dendritic cells，DC）作为专职抗原呈递细胞（antigen presenting cells，APC）在宿主免疫应答的调节中起着重要作用。DC从未成熟的抗原捕获细胞进化为成熟的抗原呈递细胞。DC对香烟烟雾诱导的炎症的相对贡献没有很好的记录。在本研究中，我们研究了香烟烟雾提取物（CSE）对DC分化、成熟和功能的调节作用。原代鼠DC从具有GM-CSF的骨髓细胞生长。采用流式细胞术检测DC的CD 11 c、MHCII、CD 86、CD 40和CD 83的表达。将鼠DC和人L428细胞与CSE共培养不同的时间段。通过测量FITC-葡聚糖摄取、细胞因子产生和在混合淋巴细胞反应中刺激T细胞活化的能力来分析功能活性。我们的研究结果表明，短期CSE刺激（~24 h）影响新分化和未成熟DC向更成熟细胞的成熟状态，如通过MHCII，CD 83，CD 86，CD 40的上调，抗原摄取能力的降低和促炎细胞因子（IL-12，IL-6和TNF-α）分泌的增加所揭示的。有趣的是，长期CSE暴露，时间和浓度依赖性，抑制功能性DC的发展。这种抑制通过CD 11 c/MHCII、CD 83、CD 86和CD 40表达、细胞因子产生和刺激T淋巴细胞的能力的下降来证明。此外，CSE显着抑制小鼠DC的内吞功能，这不是由于DC活力降低。与小鼠DC类似，人L428 DC细胞系与CSE的长期共培养时间依赖性地抑制了CD 54的表达。本研究提供了CSE通过影响DC的功能和成熟来调节DC介导的免疫应答的证据。香烟烟雾对DC功能的抑制作用可能导致对各种感染的免疫应答受损。本文的在线版本（doi：10.1186/s12931-015-0291-6）包含补充材料，可供授权用户使用。
Dendritic cells (DCs) as professional antigen presenting cells (APCs) play a critical role in the regulation of host immune responses. DCs evolve from immature, antigen-capturing cells, to mature antigen-presenting cells. The relative contribution of DCs to cigarette smoke-induced inflammation is not well documented. In the current study, we investigated a modulatory effect of cigarette smoke extract (CSE) on differentiation, maturation and function of DCs. Primary murine DCs were grown from bone marrow cells with GM-CSF. Development of DC was analyzed by expression of CD11c, MHCII, CD86, CD40 and CD83 using flow cytometry. Murine DC’s and human L428 cells were co-cultured with CSE for various periods of time. Functional activity was analyzed by measuring FITC-dextran uptake, cytokine production and the ability to stimulate T cell activation in a mixed lymphocyte reaction. Our results show that short-term CSE stimulation (~24 h) influence the maturation status of newly differentiated and immature DCs towards more mature cells as revealed by upregulation of MHCII, CD83, CD86, CD40, reduction in antigen up-take capacity and enhanced secretion of pro-inflammatory (IL-12, IL-6 and TNF-α) cytokines. Interestingly, long-term CSE exposure, time- and concentration-dependently, suppressed the development of functional DCs. This suppression was demonstrated by a decline in CD11c/MHCII, CD83, CD86 and CD40 expression, the production of cytokines and ability to stimulate T lymphocytes. Moreover, CSE significantly suppressed the endocytosis function of mouse DCs which was not due to diminished DC viability. Similar to mouse DCs, long-term co-culturing of the human L428 DC cell line with CSE time-dependently suppressed the expression of CD54. The present study provides evidence that CSE modulates DC-mediated immune responses via affecting both the function and maturation of DCs. The suppressive effects of cigarette smoke on DC function might lead to impaired immune responses to various infections. The online version of this article (doi:10.1186/s12931-015-0291-6) contains supplementary material, which is available to authorized users.