English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background The onset and progression of cervical intraepithelial neoplasia (CIN) are closely associated with the persistent infection of high-risk HPV (especially type16), which is mainly caused by immune escape. Natural killer (NK) cells play an important role against virally infected cells and tumor cells through a fine balance of signals from multiple surface receptors. Overexpression of non-MHC-I specific inhibitory receptors TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a on NK cells correlates with cellular exhaustion and immune evasion, but these receptors have not been investigated in CIN. The aim of the present study was to examine the potential role of NK cell non-MHC-I specific inhibitory receptors expression in immune escape from HPV16(+)CIN patients. Methods The subset distribution, IFN-γ and TNF-α expression levels and immunophenotype of TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a of NK cells were investigated in peripheral blood mononuclear cell samples by flow cytometry from 82 women who were HPV16(+) with CIN grades 0, I, II–III or HPV(−) CIN 0. Immunohistochemistry was applied to detect the expression of ligands for NK receptors in the cervical tissues. HPV types were identified by PCR assays. Results The HPV16(+) subjects with high-grade lesions had an increased number of circulating peripheral blood CD56 bright  NK cells with reduced functionality and IFN-γ secretion. The expression levels of the inhibitory molecules TIGIT and KLRG1 on CD56 bright  NK cells increased in parallel with increasing CIN grade. In addition, TIGIT and KLRG1 related ligands, Poliovirus receptor (PVR), N-Cadherin and E-Cadherin expression level was also elevated with increasing CIN grade. Conclusions Our results suggest that up-regulation of the inhibitory TIGIT, KLRG1 and their ligands may negatively regulate cervical CD56 bright  NK-mediated immunity to HPV16 and contribute to the progression of CIN. These results may facilitate the development of early-warning immune predictors and therapeutic strategies for HPV16(+) CIN based on the TIGIT and KLRG1 inhibitory pathways of NK cells.

Increased expression of TIGIT and KLRG1 correlates with impaired CD56bright NK cell immunity in HPV16-related cervical intraepithelial neoplasia