Loss of kindlin-3 alters the threshold for NK cell activation in human leukocyte adhesion deficiency-III

被引：20

作者：

Gruda, Raizy ^{[1
]}

Brown, Alice C. N. ^{[2
]}

Grabovsky, Valentin ^{[3
]}

Mizrahi, Saar ^{[1
]}

Gur, Chamutal ^{[1
]}

Feigelson, Sara W. ^{[3
]}

Achdout, Hagit ^{[1
]}

Bar-on, Yotam ^{[1
]}

Alon, Ronen ^{[3
]}

Aker, Memet ^{[4
]}

Davis, Daniel M. ^{[2
]}

Mandelboim, Ofer ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel

[2] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London, England

[3] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[4] Hadassah Med Ctr, Div Pediat Hematooncol, IL-91120 Jerusalem, Israel

来源：

BLOOD | 2012年 / 120卷 / 19期

基金：

英国医学研究理事会;

关键词：

NATURAL-KILLER-CELLS; INTEGRIN ACTIVATION; IMMUNOLOGICAL SYNAPSE; GRANULE POLARIZATION; INHIBITORY RECEPTORS; CYTOTOXICITY; LFA-1; DEGRANULATION; MUTATIONS; CONTACTS;

D O I：

10.1182/blood-2012-02-410795

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent evidence suggests that kindlin-3 is a major coactivator, required for most, if not all, integrin activities. Here we studied the function of kindlin-3 in regulating NK cell activation by studying a patient with kindlin-3 deficiency (leukocyte adhesion deficiency-III). We found that kindlin-3 is required for NK cell migration and adhesion under shear force. Surprisingly, we also found that kindlin-3 lowers the threshold for NK cell activation. Loss of kindlin-3 has a pronounced effect on NK cell-mediated cytotoxicity triggered by single activating receptors. In contrast, for activation through multiple receptors, kindlin-3 deficiency is overcome and target cells killed. The realization that NK cell activity is impaired, but not absent in leukocyte adhesion deficiency, may lead to the development of more efficient therapy for this rare disease. (Blood. 2012;120(19):3915-3924)

引用

页码：3915 / 3924

页数：10

共 48 条

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