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

Raizy Gruda, Alice C.N. Brown, Valentin Grabovsky, Saar Mizrahi, Chamutal Gur, Sara W. Feigelson, Hagit Achdout, Yotam Bar-on, Ronen Alon, Memet Aker, Daniel M. Davis, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)3915-3924
Number of pages10
JournalBlood
Volume120
Issue number19
DOIs
StatePublished - 8 Nov 2012

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