Cutaneous hypersensitivities to hapten are controlled by IFN-γ-upregulated keratinocyte Th1 chemokines and IFN-γ-downregulated Langerhans cell Th2 chemokines
Cutaneous hypersensitivities to hapten are controlled by IFN-γ-upregulated keratinocyte Th1 chemokines and IFN-γ-downregulated Langerhans cell Th2 chemokines
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DOI：
10.1038/jid.2008.5
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发表时间：
2008-07-01
影响因子：
6.5
通讯作者：
Tokura, Yoshiki
中科院分区：
文献类型：
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作者：
Mori, Tomoko;Kabashima, Kenji;Tokura, Yoshiki
对外源物质有即刻反应、后期反应和延迟型反应。在干扰素-伽马基因敲除(-/-)和野生型B6小鼠中，我们检测了对苦味酸(PCL)的反应以评估延迟类型反应，以及对重复挑战FITC的即时和后期反应的反应。干扰素-γ(-/-)小鼠的迟发型超敏反应受到抑制，而即刻和晚期反应增强。由于干扰素-γ(-/-)小鼠的皮肤浸润性淋巴细胞很少，我们研究了角质形成细胞和朗格汉斯细胞(LCS)产生趋化因子的情况。实时定量聚合酶链式反应分析表明，Th1类趋化因子(CXCL9和CXCL10)和Th2类趋化因子(CCL17和CCL22)分别主要来源于角质形成细胞和LC。用PCL或FITC刺激野生型小鼠角质形成细胞Th1趋化因子的表达，但不能刺激干扰素-γ(-/-)小鼠角质形成细胞产生Th2趋化因子，反复用FITC刺激干扰素-γ(-/-)小鼠LCS产生Th2趋化因子。最后，将半抗原致敏的B6小鼠的引流淋巴结细胞或致敏的绿色荧光蛋白(GFP)小鼠的淋巴细胞转移到幼稚的干扰素-γ(-/-)小鼠体内，发现CFSE+或GFP(+)淋巴细胞在受激部位的渗透较少。我们的研究表明，干扰素-γ的重要作用之一是上调角质形成细胞产生Th1趋化因子，下调LC产生Th2趋化因子。
There are immediate, late-phase, and delayed-type reactions to exogenous agents. In IFN-gamma-knockout (IFN-gamma(-/-)) and wild-type B6 mice, we examined the response to picryl chloride (PCl) for assessing delayed-type reactions, and the responses to repeatedly challenged FITC for immediate and late-phase reactions. The delayed-type hypersensitivity was depressed in IFN-gamma(-/-) mice, and the immediate and late-phase reactions were enhanced in IFN-gamma(-/-) mice. As skin-infiltrating lymphocytes were scarce at the PCl-challenged site of IFN-gamma(-/-) mice, we investigated chemokine production by keratinocytes and Langerhans cells (LCs). A real-time PCR analysis demonstrated that Th1 chemokines (CXCL9 and CXCL10) and Th2 chemokines (CCL17 and CCL22) were derived mainly from keratinocytes and LCs, respectively. Challenge with PCl or FITC augmented keratinocyte expression of Th1 chemokines in wild-type but not in IFN-gamma(-/-) mice, and Th2 chemokine production by LCs was induced by repeated FITC in IFN-gamma(-/-) mice. Finally, transfer of carboxyfluorescein diacetate succinimidyl ester (CFSE)labeled draining lymph node cells from hapten-sensitized B6 mice or lymph node cells from sensitized green fluorescent protein (GFP) mice to naive IFN-gamma(-/-) mice revealed less infiltration of CFSE+ or GFP(+) lymphocytes at the challenged site. Our study suggests that one of the crucial actions of IFN-gamma is upregulation of keratinocyte production of Th1 chemokines and downregulation of LC production of Th2 chemokines.