Cutting edge:: Opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression
Cutting edge:: Opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression
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DOI：
10.4049/jimmunol.179.3.1423
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Zou, Weiping
中科院分区：
文献类型：
--
作者：
Kryczek, Ilona;Wei, Shuang;Zou, Weiping
在本研究中，我们发现IL-17（+）CD 4（+）和IL-17（+）CD 8（+）T细胞大量存在于正常小鼠的肺和消化道粘膜。内源性和外源性IL-1显著促进TGF β和IL-6介导的IL-17（+）T细胞分化。IL-1能够在不存在IL-6的情况下刺激IL-17（+）T细胞分化。此外，尽管IL-2减少IL-17（+）T细胞分化，但IL-1完全使这种作用无效。从机制上讲，IL-1和IL-2在调节几种调节Th 17细胞分化的分子的表达中起相反的作用，这些分子包括孤儿核受体ROR γ t、IL-1受体和IL-23受体。IL-1颠覆了IL-2对这些基因转录物表达的影响。总之，我们的工作表明，IL-6是重要的，但不是必不可少的IL-17（+）T细胞的分化和IL-1在促进IL-17（+）T细胞诱导中发挥主导作用。因此，IL-17（+）T细胞库可以由微环境中的局部细胞因子谱控制。
In this report, we show IL-17(+)CD4(+) andIL-17(+)CD8(+) T cells are largely found in lung and digestive mucosa compartments in normal mice. Endogenous and exogenous IL-1 dramatically contribute to IL-17(+) T cell differentiation mediated by TGF beta and IL-6. IL-1 is capable of stimulating IL-17(+) T cell differentiation in the absence of IL-6 Furthermore, although IL-2 reduces IL-17(+) T cell differentiation, IL-1 completely disables this effect. Mechanistically, IL-1 and IL-2 play opposite roles in regulating the expression of several molecules reg- ulating Th17 cell differentiation, including the orphan nuclear receptor ROR gamma t, the IL-1 receptor, and the IL-23 receptor. IL-1 subverts the effects of IL-2 on the expression of these gene transcripts. Altogether, our work demonstrates that IL-6 is important but not indispensable for IL-17(+) T cell differentiation and that IL-1 plays a predominant role in promoting IL-17(+) T cell induction. Thus, the IL-1 7(+) T cell pool may be controlled by the local cytokine profile in the microenvironment.