Manipulating the NKG2D Receptor-Ligand Axis Using CRISPR: Novel Technologies for Improved Host Immunity

The activating immune receptor natural killer group member D (NKG2D) and its cognate ligands represent a fundamental surveillance system of cellular distress, damage or transformation. Signaling through the NKG2D receptor-ligand axis is critical for early detection of viral infection or oncogenic tr...

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Bibliographic Details
Published in:Frontiers in immunology 2021-08, Vol.12, p.712722-712722
Main Authors: Alves, Eric, McLeish, Emily, Blancafort, Pilar, Coudert, Jerome D, Gaudieri, Silvana
Format: Article
Language:English
Subjects:
cancer
CRISPR
CRISPR-Cas Systems
Disease Resistance
Disease Susceptibility
Epigenesis, Genetic
Gene Editing - methods
Genetic Therapy
Host-Pathogen Interactions - genetics
Host-Pathogen Interactions - immunology
Humans
Immunity - genetics
Immunology
Ligands
Neoplasms - etiology
NK Cell Lectin-Like Receptor Subfamily K - genetics
NK Cell Lectin-Like Receptor Subfamily K - metabolism
NK cells
NKG2D
precision medicine
Protein Binding
viral infection
Virus Diseases - etiology
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Summary:The activating immune receptor natural killer group member D (NKG2D) and its cognate ligands represent a fundamental surveillance system of cellular distress, damage or transformation. Signaling through the NKG2D receptor-ligand axis is critical for early detection of viral infection or oncogenic transformation and the presence of functional NKG2D ligands (NKG2D-L) is associated with tumor rejection and viral clearance. Many viruses and tumors have developed mechanisms to evade NKG2D recognition transcriptional, post-transcriptional or post-translational interference with NKG2D-L, supporting the concept that circumventing immune evasion of the NKG2D receptor-ligand axis may be an attractive therapeutic avenue for antiviral therapy or cancer immunotherapy. To date, the complexity of the NKG2D receptor-ligand axis and the lack of specificity of current NKG2D-targeting therapies has not allowed for the precise manipulation required to optimally harness NKG2D-mediated immunity. However, with the discovery of clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins, novel opportunities have arisen in the realm of locus-specific gene editing and regulation. Here, we give a brief overview of the NKG2D receptor-ligand axis in humans and discuss the levels at which NKG2D-L are regulated and dysregulated during viral infection and oncogenesis. Moreover, we explore the potential for CRISPR-based technologies to provide novel therapeutic avenues to improve and maximize NKG2D-mediated immunity.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.712722