The NK cell receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells.

ABSTRACT: Natural killer (NK) cell kill infected, transformed and stressed cells when an activating NK cell receptor is triggered¹. Most NK cells and some innate lymphoid cells express the activating receptor NKp46, encoded by NCR1, the most evolutionarily ancient NK cell receptor^2,3. Blockage of NKp46 inhibits NK killing of many cancer targets⁴. Although a few infectious NKp46 ligands have been identified, the endogenous NKp46 cell surface ligand is unknown. Here we show that NKp46 recognizes externalized calreticulin (ecto-CRT), which translocates from the endoplasmic reticulum (ER) to the cell membrane during ER stress. ER stress and ecto-CRT are hallmarks of chemotherapy-induced immunogenic cell death^5,6, flavivirus infection and senescence. NKp46 reco

SUBMITTER: Sen Santara S 

PROVIDER: S-EPMC10165876 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature