TY - JOUR
T1 - Loss of kindlin-3 alters the threshold for NK cell activation in human leukocyte adhesion deficiency-III
AU - Gruda, Raizy
AU - Brown, Alice C.N.
AU - Grabovsky, Valentin
AU - Mizrahi, Saar
AU - Gur, Chamutal
AU - Feigelson, Sara W.
AU - Achdout, Hagit
AU - Bar-on, Yotam
AU - Alon, Ronen
AU - Aker, Memet
AU - Davis, Daniel M.
AU - Mandelboim, Ofer
PY - 2012/11/8
Y1 - 2012/11/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84868608902&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-02-410795
DO - 10.1182/blood-2012-02-410795
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C2 - 22983444
AN - SCOPUS:84868608902
SN - 0006-4971
VL - 120
SP - 3915
EP - 3924
JO - Blood
JF - Blood
IS - 19
ER -