New Insights Into the Regulation of Natural-Killer Group 2 Member D (NKG2D) and NKG2D-Ligands: Endoplasmic Reticulum Stress and CEA-Related Cell Adhesion Molecule 1
Authors
Kaser, A
Hosomi, Shuhei
Grootjans, Joep
Huang, Yu-Hwa
Blumberg, Richard S
Publication Date
2018Journal Title
Frontiers in Immunology
ISSN
1664-3224
Publisher
Frontiers Media
Volume
9
Number
1324
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Kaser, A., Hosomi, S., Grootjans, J., Huang, Y., & Blumberg, R. S. (2018). New Insights Into the Regulation of Natural-Killer Group 2 Member D (NKG2D) and NKG2D-Ligands: Endoplasmic Reticulum Stress and CEA-Related Cell Adhesion Molecule 1. Frontiers in Immunology, 9 (1324) https://doi.org/10.3389/fimmu.2018.01324
Abstract
Natural-killer group 2 member D (NKG2D) is a well-characterized activating receptor expressed by natural killer (NK) cells, NKT cells, activated CD8+ T cells, subsets of γδ+ T cells, and innate-like T cells. NKG2D recognizes multiple ligands (NKG2D-ligands) to mount an innate immune response against stressed, transformed or infected cells. NKG2D-ligand surface expression is tightly restricted on healthy cells through transcriptional and post-transcriptional mechanisms, while transformed or infected cells express the ligands as a danger signal. Recent studies have revealed that unfolded protein response (UPR) pathways during endoplasmic reticulum (ER) stress result in up-regulation of ULBP-related protein via the PERK-ATF4-CHOP pathway, which can be linked to the pathogenesis of autoimmune diseases. Transformed cells however possess mechanisms to escape NKG2D-mediated immune surveillance, such as upregulation of carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1), a negative regulator of NKG2D-ligands. In this review, we discuss mechanisms of NKG2D-ligand regulation, with a focus on newly discovered mechanisms that promote NKG2D-ligand expression on epithelial cells, including ER stress, and mechanisms that suppress NKG2D-ligand mediated killing of cancer cells, namely by co-expression of CEACAM1.
Keywords
natural-killer group 2 member D, natural-killer group 2 member D-ligand, murine UL16-binding protein like transcript 1, UL16 binding protein 1, endoplasmic reticulum stress, CEA-related cell adhesion molecule 1
Sponsorship
Wellcome Trust Senior Investigator Award 106260/Z/14/Z, the European Research Council HORIZON2020/ERC grant no. 648889 (A.K.)
Funder references
Wellcome Trust (106260/Z/14/Z)
European Research Council (648889)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.3389/fimmu.2018.01324
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283494
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