Long noncoding RNA TANCR promotes γδT cells activation by regulating TRAIL expression in cis

Abstract

Background: γδT 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 γδT cells remains poorly studied. Results: Here, we identified the novel function of lncRNA NONHSAT196558.1 in isopentenyl pyrophosphate (IPP)-activated and -expanded γδT 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 γδT 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 γδT 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 γδT cells. Conclusion: These evidences demonstrate that TANCR play important roles in γδT cell activation. Furthermore, TANCR may be involved in the cytotoxicity of γδT cells. This study aims to further our understanding of the molecular mechanisms underlying lncRNA-mediated immune responses.