Aruna Asaf Ali Marg, New Delhi, India.
J Leukoc Biol. 2013 Apr;93(4):521-8. doi: 10.1189/jlb.0712328. Epub 2013 Jan 23.
T cells produce a number of cytokines and chemokines upon stimulation with TLR agonists in the presence or absence of TCR signals. Here, we show that secretion of neutrophil chemoattractant CXCL8 from human T cell line Jurkat in response to stimulation with TLR agonists is reduced when cell stimulation is carried out in presence of serum. Serum does not, however, inhibit TCR-activated secretion of CXCL8 nor does it down-regulate TLR-costimulated IL-2 secretion from activated T cells. The molecule that can mimic the ability to bring about suppression in CXCL8 from TLR-activated T cells is serum-borne bioactive lipid, S1P. Serum and S1P-mediated inhibition require intracellular calcium. S1P also suppresses CXCL8 secretion from peripheral blood-derived human T cells activated ex vivo with various TLR ligands. Our findings reveal a previously unrecognized role for S1P in regulating TLR-induced CXCL8 secretion from human T cells.
T 细胞在受到 TLR 激动剂刺激时，无论是否存在 TCR 信号，都会产生多种细胞因子和趋化因子。在这里，我们表明，在血清存在的情况下进行细胞刺激时，人 T 细胞系 Jurkat 对 TLR 激动剂的刺激反应中，中性粒细胞趋化因子 CXCL8 的分泌减少。然而，血清既不会抑制 TCR 激活的 CXCL8 分泌，也不会下调激活 T 细胞中 TLR 共刺激的 IL-2 分泌。能够模拟抑制 TLR 激活的 T 细胞中 CXCL8 产生能力的分子是血清来源的生物活性脂质 S1P。血清和 S1P 介导的抑制作用需要细胞内钙。S1P 还抑制外周血来源的人类 T 细胞在各种 TLR 配体体外激活后 CXCL8 的分泌。我们的发现揭示了 S1P 在调节人类 T 细胞 TLR 诱导的 CXCL8 分泌中的先前未被认识的作用。
