| First Author | Zhang Q | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 13 | Pages | 2549-66 |
| PubMed ID | 25422492 | Mgi Jnum | J:251069 |
| Mgi Id | MGI:6101726 | Doi | 10.1084/jem.20141307 |
| Citation | Zhang Q, et al. (2014) DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med 211(13):2549-66 |
| abstractText | 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. |
