TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology
TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology
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DOI：
10.1038/ni1539
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发表时间：
2007-12-01
影响因子：
30.5
通讯作者：
Cua, Daniel J.
中科院分区：
文献类型：
--
作者：
McGeachy, Mandy J.;Bak-Jensen, Kristian S.;Cua, Daniel J.
研究表明，转化生长因子-β(TGF-β)和白介素6(IL-6)是致病的产生IL-17的辅助性T细胞(T(H)-17细胞)的谱系承诺所必需的。出乎意料的是，我们发现，尽管IL-17的产生上调，但转化生长因子-β和IL-6对髓鞘反应性T细胞的刺激完全取消了它们的致病功能。用转化生长因子-β和IL-6刺激的细胞存在于脾和中枢神经系统，但它们未能上调对中枢神经系统炎症至关重要的促炎趋化因子。此外，这些细胞还产生IL-10，具有强大的抗炎活性。相反，IL-23刺激可促进IL-17和致炎趋化因子的表达，但不能促进IL-10的表达。因此，转化生长因子-β和白介素6‘推动’最初的谱系承诺，但也‘抑制’TH-17细胞的致病潜能。我们的发现表明，效应T(H)-17细胞完全获得致病功能是由IL-23介导的，而不是由转化生长因子-β和IL-6介导的。
Studies have shown that transforming growth factor-beta (TGF-beta) and interleukin 6 (IL-6) are required for the lineage commitment of pathogenic IL-17- producing T helper cells ( T(H)- 17 cells). Unexpectedly, here we found that stimulation of myelin-reactive T cells with TGF-beta plus IL-6 completely abrogated their pathogenic function despite upregulation of IL-17 production. Cells stimulated with TGF-beta plus IL- 6 were present in the spleen as well as the central nervous system, but they failed to upregulate the proinflammatory chemokines crucial for central nervous system inflammation. In addition, these cells produced IL- 10, which has potent anti-inflammatory activities. In contrast, stimulation with IL- 23 promoted expression of IL- 17 and proinflammatory chemokines but not IL-10. Hence, TGF-beta and IL- 6 'drive' initial lineage commitment but also 'restrain' the pathogenic potential of TH- 17 cells. Our findings suggest that full acquisition of pathogenic function by effector T(H)- 17 cells is mediated by IL- 23 rather than by TGF-beta and IL-6.