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首页> 外文期刊>Cytokine >Interleukin-6 expands homeostatic space for peripheral T cells
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Interleukin-6 expands homeostatic space for peripheral T cells

机译：Interleukin-6扩展了外周T细胞的稳态空间

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摘要

T cell homeostasis and survival is dependent on interleukin-7 (IL-7). Immune activation, however, downregulates IL-7 receptor expression on T cells so that T cell survival during activation must be maintained independently of IL-7. The pro-inflammatory cytokine IL-6 shares common signaling pathways with IL-7 and can promote T cell survival in vitro. But whether IL-6 promotes T cell survival and homeostasis in vivo is not clear. Notably, IL-6 overexpression results in massive plasmacytosis and autoimmunity so that an IL-6 effect on in vivo T cell survival has remained untested. To overcome this limitation, here we generated IL-6 transgenic mice on an immunoglobulin heavy chain (IgH) deficient background which rendered them B cell deficient. Notably, such IgHKOIL6Tg mice were free of any signs of inflammation or autoimmunity and remained healthy throughout the course of analysis. In these mice, we found that IL-6 overexpression significantly increased peripheral T cell numbers, but importantly without increasing thymopoiesis. Moreover, IL-6 signaled T cells maintained their na?ve phenotype and did not express activation/memory markers, suggesting that increased T cell numbers were due to increased T cell survival and not because of expansion of activated T cells. Mechanistically, we found that IL-6 signaling induced expression of pro-survival factors Mcl-1 and Pim-1/-2 but not Bcl-2. Thus, IL-6 is a T cell homeostatic cytokine that expands T cell space and can maintain the na?ve T cell pool.
机译：T细胞稳态和生存取决于白介素7（IL-7）。但是，免疫激活会下调T细胞上的IL-7受体表达，因此激活期间的T细胞存活必须独立于IL-7维持。促炎细胞因子IL-6与IL-7共有共同的信号传导途径，并且可以促进体外T细胞存活。但是，IL-6是否在体内促进T细胞存活和体内稳态尚不清楚。值得注意的是，IL-6的过度表达导致大量浆细胞增多和自身免疫，因此尚未测试IL-6对体内T细胞存活的影响。为了克服这个限制，在这里我们在免疫球蛋白重链（IgH）缺陷的背景上产生了IL-6转基因小鼠，这使它们成为B细胞缺陷。值得注意的是，这种IgHKOIL6Tg小鼠没有任何炎症或自身免疫迹象，并在整个分析过程中保持健康。在这些小鼠中，我们发现IL-6过表达显着增加了外周T细胞的数量，但重要的是没有增加胸腺生成。此外，IL-6信号转导的T细胞保持其幼稚的表型，并且不表达激活/记忆标记，这表明增加的T细胞数量是由于T细胞存活时间延长，而不是由于活化T细胞的扩增所致。从机理上讲，我们发现IL-6信号传导诱导了生存因子Mcl-1和Pim-1 / -2的表达，但不诱导Bcl-2的表达。因此，IL-6是一种T细胞稳态细胞因子，可扩展T细胞空间并可以维持幼稚的T细胞池。

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