Title |
DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity
|
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Published in |
The Journal of Experimental Medicine, November 2014
|
DOI | 10.1084/jem.20141307 |
Pubmed ID | |
Authors |
Qian Zhang, Christopher G. Dove, Jyh Liang Hor, Heardley M. Murdock, Dara M. Strauss-Albee, Jordan A. Garcia, Judith N. Mandl, Rachael A. Grodick, Huie Jing, Devon B. Chandler-Brown, Timothy E. Lenardo, Greg Crawford, Helen F. Matthews, Alexandra F. Freeman, Richard J. Cornall, Ronald N. Germain, Scott N. Mueller, Helen C. Su |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 2% |
Unknown | 131 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 34 | 26% |
Researcher | 24 | 18% |
Student > Doctoral Student | 10 | 8% |
Student > Master | 10 | 8% |
Student > Bachelor | 8 | 6% |
Other | 21 | 16% |
Unknown | 26 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 28 | 21% |
Agricultural and Biological Sciences | 27 | 20% |
Medicine and Dentistry | 22 | 17% |
Biochemistry, Genetics and Molecular Biology | 19 | 14% |
Engineering | 2 | 2% |
Other | 4 | 3% |
Unknown | 31 | 23% |