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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.