IL-10-producing Langerhans cells and regulatory T cells are responsible for depressed contact hypersensitivity in grafted skin.
IL-10-producing Langerhans cells and regulatory T cells are responsible for depressed contact hypersensitivity in grafted skin.
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DOI：
10.1038/jid.2008.304
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
Ryutaro Yoshiki;K. Kabashima;K. Sugita;K. Atarashi;T. Shimauchi;Y. Tokura
中科院分区：
文献类型：
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作者：
Ryutaro Yoshiki;K. Kabashima;K. Sugita;K. Atarashi;T. Shimauchi;Y. Tokura
虽然皮肤移植是一种常见的外科手术技术，移植皮肤的免疫状态仍不清楚。一个实验模型表明，当小鼠通过全层移植皮肤用半抗原致敏时，小鼠接触性超敏反应（CHS）的发展受到抑制。我们探讨了这种低敏感性的免疫学机制，重点是朗格汉斯细胞（LC）的命运。当将FITC应用于移植皮肤时，携带FITC的LC能够迁移到引流淋巴结。从移植皮肤分离的表皮细胞悬浮液产生大量的IL-10，如通过实时PCR评估的。从致敏小鼠连续转移免疫淋巴结细胞以抗原特异性方式抑制受体的CHS反应。从淋巴结细胞中纯化的CD 4 + CD 25 + T细胞而不是CD 4 + CD 25 −T细胞负责这种抑制。最后，我们检测到核因子κ-B配体受体激活因子（RANKL）在移植皮肤中的高表达，并发现重组RANKL刺激LC产生IL-10。这些研究结果表明，通过移植皮肤的CHS的脱敏是不是仅仅归因于LC数量的减少，但IL-10产生的LC通过诱导调节性T细胞发挥下调作用。
Although skin grafting is a common surgical technique, the immunological state of grafted skin remains unelucidated. An experimental model has shown that the development of murine contact hypersensitivity (CHS) is depressed when mice are sensitized with a hapten through full-thickness grafted skin. We explored the immunological mechanisms underlying this hyposensitization, focusing on the fate of Langerhans cells (LCs). When FITC was applied to grafted skin, FITC-bearing LCs were capable of migrating to the draining lymph nodes. Epidermal cell suspensions isolated from the grafted skin produced a high amount of IL-10 as assessed by real-time PCR. Adoptive transfer of immune lymph node cells from the sensitized mice suppressed the CHS response of recipients in an antigen-specific manner. CD4+CD25+but not CD4+CD25−T cells purified from lymph node cells were responsible for this suppression. Finally, we detected high expression of receptor activators of nuclear factor κ-B ligand (RANKL) in the grafted skin, and found that recombinant RANKL stimulated LCs to produce IL-10. These findings suggest that the hyposensitization of CHS through the grafted skin is not attributable merely to the reduction of LC number but that IL-10-producing LCs exert a downmodulatory effect by inducing regulatory T cells.