DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity.
DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity.
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DOI：
10.1084/jem.20141307
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发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Su HC
中科院分区：
文献类型：
--
作者：
Zhang Q;Dove CG;Hor JL;Murdock HM;Strauss-Albee DM;Garcia JA;Mandl JN;Grodick RA;Jing H;Chandler-Brown DB;Lenardo TE;Crawford G;Matthews HF;Freeman AF;Cornall RJ;Germain RN;Mueller SN;Su HC
Zhang et al. show that DOCK8-deficient T and NK cells develop cell and nuclear shape abnormalities that do not impair chemotaxis but contribute to a form of cell death they term cytothripsis. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells resulting in impaired immune response to skin infection. 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.
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影响因子：
32.4
作者：
Honda T;Egen JG;Lämmermann T;Kastenmüller W;Torabi-Parizi P;Germain RN
通讯作者：
Germain RN
影响因子：
20.3
作者：
Crawford, Greg;Enders, Anselm;Cornall, Richard J.
通讯作者：
Cornall, Richard J.
影响因子：
3.1
作者：
Goel, N;Docherty, JJ;Rosenthal, KS
通讯作者：
Rosenthal, KS
DOI：
10.1073/pnas.1010249107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Guo, Fukun;Hildeman, David;Zheng, Yi
通讯作者：
Zheng, Yi
影响因子：
20.3
作者：
Imai, K;Morio, T;Nonoyama, S
通讯作者：
Nonoyama, S