LncRNA-ENST00000421645 Upregulates Kank1 to Inhibit IFN-γ Expression and Promote T Cell Apoptosis in Neurosyphilis

Abstract

Long non-coding RNAs are involved in many infectious diseases. Our previous studies showed that lncRNA-ENST00000421645 expression is increased in T lymphocytes of neurosyphilis patients compared to healthy controls. However, whether lncRNA-ENST00000421645 has biological functions remains unclear. The current study was undertaken to understand the mechanism of lncRNA-ENST00000421645 in T lymphocyte function in neurosyphilis patients. The lncRNA-ENST00000421645 pull-down assay showed that lncRNA-ENST00000421645 acted on the acetylase NAT10. The chromatin immunoprecipitation (ChIP)-PCR results showed that lncRNA-ENST00000421645 promoted the acetylation of histone H3K27 adjacent to the Kank1 promoter, thereby promoting Kank1 protein expression. Kank1 promotes 14-3-3 protein expression, inhibits NF-kB activation, inhibits IFN-γ secretion by T lymphocytes, and promotes T lymphocyte apoptosis. Taken together, our findings suggest a novel mechanism that LncRNA-ENST00000421645 upregulates Kank1 to inhibit IFN-γ expression and promote T cell apoptosis in neurosyphilis.

Identification of single nucleotide polymorphisms (SNPs) associated with chronic graft-versus-host disease in patients undergoing allogeneic hematopoietic cell transplantation

“…It is therefore conceivable that KANK1 homozygous mutations in its regulatory sequence could be responsible for impaired tissue reformation and fibrosis characteristic of the third phase of cGVHD. In addition, since KANK1 function seems to be linked to the JAK pathway and has been shown to inhibit IFN-γ to promote T cell apoptosis further investigation to determine its validity as a drug target candidate for the treatment of cGVHD is warranted [ 51 ].…”

New mechanism of LncRNA: In addition to act as a ceRNA

“…LncRNAs regulate the transcription of many different functional genes through histone acetylation, and therefore produce a variety of effects. And there have been numerous experiments demonstrating that lncRNAs are closely related to tumour cell proliferation and metastasis, macrophage polarization, and apoptosis during cellular senescence under this mechanism [ [74] , [75] , [76] ].…”

CARE-NS, a research strategy for neurosyphilis

“…Other studies have found that the number of Treg cells in the CSF is reduced such that they are not sufficient to inhibit T-cell-mediated inflammation and subsequent injury to the meninges, brain parenchyma, spinal cord, and other tissues (37). Recent studies have also found that lncRNA-ENST00000421645 promotes T-cell apoptosis in patients with neurosyphilis by mediating IFN-γ production through interaction with PCM1 protein (38). An additional study showed that T. pallidum can adhere to the host cell surface and capillary lining through mucopolysaccharide enzymes, which destroy mucopolysaccharide-rich blood vessels.…”