Th17 (IFNγ- IL17+) CD4+ T Cells Generated After Burn Injury May Be a Novel Cellular Mechanism for Postburn Immunosuppression
Th17 (IFNγ- IL17+) CD4+ T Cells Generated After Burn Injury May Be a Novel Cellular Mechanism for Postburn Immunosuppression
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DOI：
10.1097/ta.0b013e31820d18a6
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发表时间：
2011-03-01
影响因子：
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通讯作者：
Cairns, Bruce A.
中科院分区：
文献类型：
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作者：
Neely, Crystal J.;Maile, Robert;Cairns, Bruce A.
背景：烧伤后免疫抑制反应的启动和控制机制尚不清楚。白细胞介素-17 （IL-17）分泌Th17(干扰素[IFN] γ (-) IL17(+))细胞是CD4(+) T细胞的一个新子集，与微弱的促炎反应相关，可拮抗促炎Th1 (IFN γ (+) IL17(-))反应。鉴于转化生长因子- β和il - 6介导Th17细胞的发育，我们假设烧伤损伤可能产生介导烧伤后免疫抑制的Th17细胞。方法：雌性C57BL/6小鼠体表面积20%烧伤后，分别于伤后3天、7天、14天采集创面引流淋巴结。磁选择富集CD4(+) T细胞，流式细胞术检测CD3(+)CD4(+) T细胞内il - 17和IFN γ。将纯化的CD3(+)CD4(+) T细胞与Th17（-）极化的il - 6和转化生长因子- β一起培养4天，再次用流式细胞术检测CD4(+) T细胞内的il - 17和IFN γ。结果：各时间点烧伤小鼠预成型Th17细胞数量和百分比均显著高于假手术小鼠。此外，烧伤小鼠Th17细胞与Th1细胞的比例始终显著高于假手术小鼠。这些差异在体外Th17极化条件下被消除。CD4(+) T细胞从未同时产生IL17和IFN γ。结论：本实验结果首次证明了烧伤后Th17细胞(IFN γ (-) IL17(+))是自发生成的。鉴于Th17细胞(IFN γ (-) IL17(+))对Th1细胞（IFN+ IL17(-)）具有拮抗作用，这些结果提示了一种启动和控制烧伤后免疫抑制的新机制，值得进一步研究。
Background: The mechanism responsible for initiating and controlling the immunosuppressive response after burn injury remains unknown. Interleukin-17 (IL-17) secreting Th17 (interferon [IFN]gamma(-) IL17(+)) cells are a novel subset of CD4(+) T cells associated with a weak, proinflammatory response that antagonizes the proinflammatory Th1 (IFN gamma(+) IL17(-)) response. Given that transforming growth factor-beta and IL6 mediate Th17 cell development, we hypothesized that burn injury may generate Th17 cells that could mediate postburn immunosuppression.Methods: After a 20% total body surface area burn in female C57BL/6 mice, wound-draining lymph nodes were harvested 3 days, 7 days, or 14 days after injury. CD4(+) T cells were enriched by magnetic selection, and flow cytometry was used to identify intracellular IL17 and IFN gamma in CD3(+)CD4(+) T cells. Additional purified CD3(+)CD4(+) T cells were cultured with Th17(-) polarizing IL6 and transforming growth factor-beta for 4 days, and flow cytometry was again used to identify intracellular IL17 and IFN gamma in CD4(+) T cells.Results: The number and percentage of preformed Th17 cells was significantly greater in burn mice compared with sham at all time points. In addition, the ratio of Th17 cells to Th1 cells was always significantly higher in burn mice compared with sham. These differences were eliminated in Th17 polarizing conditions in vitro. CD4(+) T cells never generated both IL17 and IFN gamma.Conclusion: These results demonstrate for the first time that Th17 cells (IFN gamma(-) IL17(+)) are spontaneously generated after burn injury. Given that Th17 cells (IFN gamma(-) IL17(+)) are antagonistic to Th1 (IFN+ IL17(-)) cells, these results suggest a novel mechanism for initiating and controlling postburn immunosuppression that deserves further investigation.