Senescent Cells Evade Immune Clearance Via HLA-E-mediated NK and CD8 T Cell Inhibition

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jun 5

PMID 31160572

Citations 227

Authors

Branca I Pereira

Oliver P Devine

Milica Vukmanovic-Stejic

Emma S Chambers

Priya Subramanian

Neil Patel

Alex Virasami

Neil J Sebire

Veronica Kinsler

Alexis Valdovinos

Claude Jourdan LeSaux

Joao F Passos

Antony Antoniou

Malcom H A Rustin

Judith Campisi

Arne N Akbar

Affiliations

Soon will be listed here.

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, blocking the interaction between HLA-E and NKG2A boosts immune responses against senescent cells in vitro. We thus propose that increased HLA-E expression contributes to persistence of senescent cells in tissues, thereby suggesting a new strategy for eliminating senescent cells during ageing.

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