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…

• FF
  Foundation for the National Institutes of Health

  Awards: AG051729, AG052744
• BI
  Buck Institute for Research on Aging
• NI
  National Institute for Health and Care Research
• UC
  University College London
• NI
  National Institutes of Health

  Award: AG051729
• MR
  Medical Research Council

  Awards: MR/N017749/1, MR/M003833/1, MR/P00184X/1, MR/M003833/1, MR/P00184X/1
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BB/K017314/1, BB/H022384/1
• IO
  Institute of Genetics