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Long noncoding RNA derived from CD244 signaling epigenetically controls CD8⁺ T-cell immune responses in tuberculosis infection
- Wang, Yang, Zhong, Huiling, Xie, Xiaodan, Chen, Crystal Y., Huang, Dan, Shen, Ling, Zhang, Hui, Chen, Zheng W., Zeng, Gucheng
- Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.29 pp. E3883
- CD8-positive T-lymphocytes, chromatin, immune response, interferon-gamma, loci, non-coding RNA, tuberculosis, tumor necrosis factor-alpha
- Tuberculosis (TB) infection induces up-regulation of T cell-inhibitory molecules on CD8 ⁺ T cells, which may induce impairment of CD8 ⁺ T-cell immunity. However, how T cell-inhibitory molecules regulate CD8 ⁺ T-cell immune responses during TB infection remains unclear. Here, we demonstrate that CD244, a T cell-inhibitory molecule, mediates inhibition of IFN-γ and TNF-α expression through inducing expression of a long noncoding RNA (lncRNA)-CD244. lncRNA-CD244 physically interacts with a chromatin-modification enzyme, enhancer of zeste homolog 2 (EZH2), and mediates modification of a more repressive chromatin state in infg and tnfa loci. Knock down of lncRNA-CD244 significantly enhances IFN-γ and TNF-α expression and improves protective immunity of CD8 ⁺ T cells. This study therefore uncovers a previously unknown mechanism for T-cell immune responses regulated by lncRNA during TB infection.