Src kinases central to T-cell receptor signaling regulate TLR-activated innate immune responses from human T cells:

Innate Immunity

NaveenSharma¹ 

关键词: Toll-like receptor;    Src kinases;    T-cell receptor;    innate immune response;    human T cells;   

DOI  :  10.1177/1753425916632305

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

TLRs have a fundamental role in immunity. We have recently reported that stimulation of TLR2 and TLR5 in freshly isolated and activated human T cells with microbial ligands without concomitant activation through the TCR brings about secretion of neutrophil chemoattractant, CXCL8, and effector cytokine, IFN-γ, respectively. However, the mechanism of TLR signaling in T cells has not been worked out. Here, we show that the Src family kinases, p56lck (Lck) and p59fyn (Fyn), which are essential for activation of T cells through the TCR, are also critical for signal transduction through TLRs in human T cells. The secretion of CXCL8 following stimulation of the model human T cell line, Jurkat, with the TLR5 ligand, flagellin, was reduced in presence of the Src-kinase inhibitor, PP2 and specific inhibitors of Lck and Fyn. These inhibitors suppressed generation of activated JNK and p38, which were both required for TLR-induced CXCL8 production. The Lck-deficient derivative of Jurkat, JCam1.6, responded poorly to T...

【 授权许可】

CC BY