DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity

被引：130

作者：

Zhang, Qian ^{[1
]}

Dove, Christopher G. ^{[1
]}

Hor, Jyh Liang ^{[5
,6
]}

Murdock, Heardley M. ^{[1
]}

Strauss-Albee, Dara M. ^{[1
]}

Garcia, Jordan A. ^{[1
]}

Mandl, Judith N. ^{[2
]}

Grodick, Rachael A. ^{[1
]}

Jing, Huie ^{[1
]}

Chandler-Brown, Devon B. ^{[1
]}

Lenardo, Timothy E. ^{[1
]}

Crawford, Greg ^{[7
]}

Matthews, Helen F. ^{[3
]}

Freeman, Alexandra F. ^{[4
]}

Cornall, Richard J. ^{[7
]}

Germain, Ronald N. ^{[2
]}

Mueller, Scott N. ^{[5
,6
]}

Su, Helen C. ^{[1
]}

机构：

[1] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA

[2] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA

[3] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA

[4] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA

[5] Univ Melbourne, Dept Microbiol & Immunol, Peter Doherty Inst Infect & Immun, Melbourne, Vic 3010, Australia

[6] Univ Melbourne, ARC Ctr Excellence Adv Mol Imaging, Melbourne, Vic 3010, Australia

[7] Univ Oxford, Nuffield Dept Med, MRC Human Immunol Unit, Oxford OX3 7BN, England

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 13期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

ALDRICH-SYNDROME PROTEIN; HERPES-SIMPLEX-VIRUS; MEMORY T-CELLS; VARICELLA-ZOSTER-VIRUS; LEUKOCYTE MIGRATION; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSES; IN-VITRO; RM CELLS; TISSUE;

D O I：

10.1084/jem.20141307

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：2549 / 2566

页数：18

共 78 条

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