DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T and NK cells migrate through confined spaces, they develop cell shape and nuclear deformation abnormalities that do not impair chemotaxis but contribute to a distinct form of catastrophic cell death we term cytothripsis. Such defects arise during lymphocyte migration in collagen-dense tissues when DOCK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structures. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells, which in turn impairs control of herpesvirus skin infections. Our results establish that DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin.
CITATION STYLE
Zhang, Q., Dove, C. G., Hor, J. L., Murdock, H. M., Strauss-Albee, D. M., Garcia, J. A., … Su, H. C. (2014). DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. Journal of Experimental Medicine, 211(13), 2549–2566. https://doi.org/10.1084/jem.20141307
Mendeley helps you to discover research relevant for your work.