Martin Bruno, Hirota Keiji, Cua Daniel J, Stockinger Brigitta, Veldhoen Marc
Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Immunity. 2009 Aug 21;31(2):321-30. doi: 10.1016/j.immuni.2009.06.020. Epub 2009 Aug 13.
Gammadelta T cells are an innate source of interleukin-17 (IL-17), preceding the development of the adaptive T helper 17 (Th17) cell response. Here we show that IL-17-producing T cell receptor gammadelta (TCRgammadelta) T cells share characteristic features with Th17 cells, such as expression of chemokine receptor 6 (CCR6), retinoid orphan receptor (RORgammat), aryl hydrocarbon receptor (AhR), and IL-23 receptor. AhR expression in gammadelta T cells was essential for the production of IL-22 but not for optimal IL-17 production. In contrast to Th17 cells, CCR6(+)IL-17-producing gammadelta T cells, but not other gammadelta T cells, express Toll-like receptors TLR1 and TLR2, as well as dectin-1, but not TLR4 and could directly interact with certain pathogens. This process was amplified by IL-23 and resulted in expansion, increased IL-17 production, and recruitment of neutrophils. Thus, innate receptor expression linked with IL-17 production characterizes TCRgammadelta T cells as an efficient first line of defense that can orchestrate an inflammatory response to pathogen-derived as well as environmental signals long before Th17 cells have sensed bacterial invasion.
γδ T细胞是白细胞介素-17（IL-17）的先天性来源，早于适应性辅助性T细胞17（Th17）细胞反应的发展。在此我们表明，产生IL-17的T细胞受体γδ（TCRγδ）T细胞与Th17细胞具有共同特征，如趋化因子受体6（CCR6）、视黄酸孤儿受体（RORγt）、芳烃受体（AhR）和IL-23受体的表达。γδ T细胞中AhR的表达对于IL-22的产生至关重要，但对于最佳IL-17的产生并非必需。与Th17细胞不同，产生IL-17的CCR6(+)γδ T细胞而非其他γδ T细胞表达Toll样受体TLR1和TLR2以及dectin-1，但不表达TLR4，并且能够直接与某些病原体相互作用。这一过程被IL-23放大，导致细胞扩增、IL-17产生增加以及中性粒细胞募集。因此，与IL-17产生相关的先天性受体表达将TCRγδ T细胞表征为一种有效的第一道防线，它能够在Th17细胞感知细菌入侵之前很久就协调针对病原体衍生信号以及环境信号的炎症反应。
