The Influence of Excessive IL-6 Production In Vivo on the Development and Function of Foxp3+ Regulatory T Cells
The Influence of Excessive IL-6 Production In Vivo on the Development and Function of Foxp3+ Regulatory T Cells
复制标题
DOI：
10.4049/jimmunol.0903314
复制
发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Naka, Tetsuji
中科院分区：
文献类型：
--
作者：
Fujimoto, Minoru;Nakano, Mayumi;Naka, Tetsuji
IL-6 是一种促炎细胞因子，其过量产生与多种炎症性疾病有关。最近的体外分析表明，IL-6 是决定 Foxp3(+) 调节性 T 细胞 (Treg) 和 Th17 细胞之间平衡的关键细胞因子。然而，目前尚不清楚体内过多的IL-6产生是否会改变Foxp3(+) Tregs的发育和功能。在本研究中，我们分析了血清 IL-6 水平持续升高的 IL-6 转基因 (Tg) 小鼠。有趣的是，在IL-6 Tg小鼠中，虽然外周淋巴器官增大，T细胞表现出激活表型，但与野生型小鼠相比，Tregs不但没有减少，反而增加了。此外，来自 Tg 小鼠的 Tregs 通常会抑制体外幼稚 T 细胞的增殖。此外，将 Tregs 与初始 CD4 T 细胞共转移到 SCID-IL-6 Tg 小鼠中，与转移到对照 SCID 小鼠中一样成功地抑制结肠炎。这些结果表明IL-6的过量产生不会抑制体内Foxp3(+) Tregs的发育或功能。然而，当仅转移初始CD4 T细胞时，与SCID小鼠相比，从SCID-IL-6 Tg小鼠中检索到的Foxp3(+) Tregs减少。此外，与野生型小鼠相比，IL-6 Tg 小鼠中 Foxp3(+) Tregs 的 Helios(-) 亚群（最近被定义为胸腺外 Tregs）显着减少。总的来说，这些结果表明体内过量产生的 IL-6 抑制初始 T 细胞的诱导性 Treg 生成，但不影响天然 Treg 的发育和功能。免疫学杂志，2011，186：32-40。
IL-6 is a proinflammatory cytokine and its overproduction is implicated in a variety of inflammatory disorders. Recent in vitro analyses suggest that IL-6 is a key cytokine that determines the balance between Foxp3(+) regulatory T cells (Tregs) and Th17 cells. However, it remains unclear whether excessive IL-6 production in vivo alters the development and function of Foxp3(+) Tregs. In this study, we analyzed IL-6 transgenic (Tg) mice in which serum IL-6 levels are constitutively elevated. Interestingly, in IL-6 Tg mice, whereas peripheral lymphoid organs were enlarged, and T cells exhibited activated phenotype, Tregs were not reduced but rather increased compared with wild-type mice. In addition, Tregs from Tg mice normally suppressed proliferation of naive T cells in vitro. Furthermore, Tregs cotransferred with naive CD4 T cells into SCID-IL-6 Tg mice inhibited colitis as successfully as those transferred into control SCID mice. These results indicate that overproduction of IL-6 does not inhibit development or function of Foxp3(+) Tregs in vivo. However, when naive CD4 T cells alone were transferred, Foxp3(+) Tregs retrieved from SCID-IL-6 Tg mice were reduced compared with SCID mice. Moreover, the Helios(-) subpopulation of Foxp3(+) Tregs, recently defined as extrathymic Tregs, was significantly reduced in IL-6 Tg mice compared with wild-type mice. Collectively, these results suggest that IL-6 overproduced in vivo inhibits inducible Treg generation from naive T cells, but does not affect the development and function of natural Tregs. The Journal of Immunology, 2011, 186: 32-40.