Abstract
Backgroundγδ T cells are an important subset of T lymphocytes that play important roles in innate and adaptive immunity via the secretion of various cytokines. Previous studies have found that long noncoding RNAs (lncRNAs) are critical regulators that contribute to the development of immune cells. However, the functions of lncRNAs in the γδ T cells remains poorly studied.ResultsHere, we identified the novel function of lncRNA NONHSAT196558.1 in isopentenyl pyrophosphate (IPP)-activated and -expanded γδ T cells using RNA-seq. As it functioned as an activating noncoding RNA of tumor necrosis factor related apoptosis-inducing ligand (TRAIL), an important cytotoxic cytokine that expressed by γδ T cells in responding to various infectious agents, we named this lncRNA as TANCR. Secondly, the expression of TANCR was found to be positively correlated with TRAIL expression in IPP activated γδ T cells. In addition, TANCR was confirmed to localized both in nucleus and cytoplasm. Finally, a loss-of-function was conducted by using siRNA/ASO or CRISPR/Cas9 system to knockdown or knockout TANCR, and confirmed that silencing of TANCR inhibits TRAIL expression in several kinds of cells, including HEK293T cells, Jurkat cells, and primary γδ T cells.ConclusionThese evidences demonstrate that TANCR play important roles in γδ T cell activation. Furthermore, TANCR may be involved in the cytotoxicity of γδ T cells. This study aims to further our understanding of the molecular mechanisms underlying lncRNA-mediated immune responses.
Highlights
Background γδT cells are a subset of T lymphocytes that are classified as CD3 and T cell receptor (TCR) γδ double positive [1, 2]. γδ T cells occupy 5–10 percentage of peripheral T cells, while γδ T cells can be as high as 50% of total CD3+ T cells in some mucosal tissues [3, 4]. γδ T cells play critical roles in defending against various infections
Γδ T cells were activated by isopentenyl pyrophosphate (IPP), and we investigated the differentially expressed genes including Long noncoding RNA (lncRNA) and mRNAs in the activated of γδ T cells compared with fresh γδ T cells using RNAseq
Bioinformatic analysis was performed to predict lncRNA–mRNA pairs that regulated in cis, we found that the lncRNA NONHSAT196558.1 expressed much higher in IPP-activated γδ T cells, and positively correlated with tumor necrosis factor related apoptosis-inducing ligand (TRAIL, known as TNFSF10) expression
Summary
Background γδT cells are a subset of T lymphocytes that are classified as CD3 and T cell receptor (TCR) γδ double positive [1, 2]. γδ T cells occupy 5–10 percentage of peripheral T cells, while γδ T cells can be as high as 50% of total CD3+ T cells in some mucosal tissues [3, 4]. γδ T cells play critical roles in defending against various infections. Micro-RNAs are a well-known noncoding RNA type that regulates gene expression by binding the 3′ untranslated region of a target gene [14]. Previous studies have showed the evidence that lncRNA regulate various genes in the immune system. LncRNA lnc-DC regulates the differentiation of dendritic cell via binding to signal transducer and activator of transcription 3 [20]. Long intergenic ncRNA EPS acts as an inhibitor in the inflammatory response in macrophages [21]. Taken together, these evidences strongly indicate that lncRNAs act as critical regulators in the immune system. Exploring the lncRNA regulation network in γδ T cells may help us better understand the function of lncRNA in γδ T cell biology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
