Positive and negative regulation of the IL-27 receptor during lymphoid cell activation
Positive and negative regulation of the IL-27 receptor during lymphoid cell activation
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DOI：
10.4049/jimmunol.174.12.7684
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Hunter, CA
中科院分区：
文献类型：
--
作者：
Villarino, AV;Larkin, J;Hunter, CA
以前的报道集中在IL-27促进初始T细胞反应的能力上，但目前的研究发现，IL-27R的配体特异性成分WSX-1在这些细胞上的表面表达水平很低，而在效应和记忆CD4(+)和CD8(+)T细胞上的表达水平最高。因此，在感染弓形虫的过程中，体内T细胞的激活与WSX-1的表达增强有关，在体外，TCR结扎可以诱导WSX-1的表达，而与启动时存在的极化(Th1/Th2)环境无关。然而，虽然这些数据证实有丝分裂刺激促进T细胞表达WSX-1，但在急性弓形虫病期间，NK细胞和NKT细胞的激活促使WSX-1水平降低。总之，这些研究表明，IL-2可以通过激活的CD4(+)T细胞抑制WSX-1的表达，这些研究表明，IL-27R的表面水平可以受到与淋巴细胞激活相关的正负信号的调节。此外，由于WSX-1在静息NK细胞、静息NKT细胞、效应T细胞、调节性T细胞和记忆T细胞上的高水平明显，目前的工作表明IL-27可以影响天然免疫和获得性免疫的多种效应细胞。
Previous reports have focused on the ability of IL-27 to promote naive T cell responses but the present study reveals that surface expression of WSX-1, the ligand-specific component of the IL-27R, is low on these cells and that highest levels are found on effector and memory CD4(+) and CD8(+) T cells. Accordingly, during infection with Toxoplasma gondii, in vivo T cell activation is associated with enhanced expression of WSX-1, and, in vitro, TCR ligation can induce expression of WSX-1 regardless of the polarizing (Th1/Th2) environment present at the time of priming. However, while these data establish that mitogenic stimulation promotes expression of WSX-1 by T cells, activation of NK cells and NKT cells prompts a reduction in WSX-1 levels during acute toxoplasmosis. Together, with the finding that IL-2 can suppress expression of WSX-1 by activated CD4(+) T cells, these studies indicate that surface levels of the IL-27R can be regulated by positive and negative signals associated with lymphoid cell activation. Additionally, since high levels of WSX-1 are evident on resting NK cells, resting NKT cells, effector T cells, regulatory T cells, and memory T cells, the current work demonstrates that IL-27 can influence multiple effector cells of innate and adaptive immunity.