Senescent cells evade immune clearance via HLA-E-mediated NK and CD8⁺ T cell inhibition.

ABSTRACT: Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with the inhibitory receptor NKG2A expressed by NK and highly differentiated CD8⁺ T cells to inhibit immune responses against senescent cells. HLA-E expression is induced by senescence-associated secretary phenotype-related pro-inflammatory cytokines, and is regulated by p38 MAP kinase signalling in vitro. Consistently, HLA-E expression is increased on senescent cells in human skin sections from old individuals, when compared with those from young, and in human melanocytic nevi relative to normal skin. Lastly,

SUBMITTER: Pereira BI 

PROVIDER: S-EPMC6547655 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature