Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns.
Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns.
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DOI：
10.1371/journal.pone.0158993
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cap AP
中科院分区：
文献类型：
--
作者：
Schwacha MG;Rani M;Nicholson SE;Lewis AM;Holloway TL;Sordo S;Cap AP
已有研究表明，γ-增量T细胞在损伤的早期免疫炎症反应中具有重要作用，不受感染的影响。这种独特的T细胞群起着调节细胞运输和释放细胞因子和生长因子的作用。我们认为，这种无菌炎症反应在一定程度上与烧伤等重大损伤产生的损伤相关分子模式(DAMP)有关，并通过Toll样受体(Toll-like Receptor，TLR)介导。目前尚不清楚DAMPS是否可以激活驻留在皮肤中的γδT细胞。用酶消化法从雄性C57BL/6小鼠皮肤中分离出γ-Delta T细胞。用超声和离心法从小鼠肝脏分离线粒体，产生线粒体阻滞剂(MTDS)。将真皮γδT细胞与MTDS(0~5 0 0μg/ml)孵育2 4h，收集细胞和培养上清进行分析。MTDS激活了真皮γδT细胞，体外暴露后TLR2和TLR4表达增加。MTDS还可诱导γδT细胞产生炎性细胞因子(IL-1、IL-6)和生长因子(PDGFR、VEGFs)。这些发现支持了组织/细胞损伤后释放的MTDS能够激活真皮γδT细胞的概念。我们认为，这种独特的T细胞群的激活在无菌炎症的启动中是核心的，也有助于随后的愈合过程。
Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0–500 μg/ml) for 24 hr and cells and supernatants were collected for analysis. MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1β, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.