Abstract
Integrins are transmembrane receptors associated with adhesion and migration and are often highly differentially expressed receptors amongst natural killer cell subsets in microenvironments. Tissue resident natural killer cells are frequently defined by their differential integrin expression compared to other NK cell subsets, and integrins can further localize tissue resident NK cells to tissue microenvironments. As such, integrins play important roles in both the phenotypic and functional identity of NK cell subsets. Here we review the expression of integrin subtypes on NK cells and NK cell subsets with the goal of better understanding how integrin selection can dictate tissue residency and mediate function from the nanoscale to the tissue environment.
Highlights
NK cell subsets are defined by surface receptors, especially integrins, transcription factors, and intracellular effector molecules
It should be noted that the example of VLA-4 and LFA-1 in this case is likely distinct from chemotaxis or 3D cell migration in a tissue microenvironment, in which integrins play different roles or may even be redundant [50, 134]
With a greater understanding of the importance of trNKs within tissues comes a better appreciation of the cross length-scale role of integrins in their regulation
Summary
Integrins in immunology are often described as single subunits as they are detected this way by flow cytometry, RNA-Seq and proteomic analyses. It should be noted that the example of VLA-4 and LFA-1 in this case is likely distinct from chemotaxis or 3D cell migration in a tissue microenvironment, in which integrins play different roles or may even be redundant [50, 134] Regardless, this example highlights the importance of using measurements such as integrin activation, signaling, and localization in addition to cell surface expression when defining the significance of integrin expression on cellular subsets. As the upregulation of their expression is linked to the acquisition of a transcriptional signature associated with tissue resident T cells, it is unclear what the local signals are that drive these changes, but they likely include chemokines, cell adhesion molecules, and ECM components. These technological advances will enable us to link integrin adhesion behaviors on a molecular level to single cell behaviors and population behaviors and are primed to give us access to the molecular basis of NK cell tissue residency, migration and development
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