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

Recent evidence suggests that kindlin-3 is a major coactivator, required for most, if not all, integrin activities. Here we stud-led the function of klndlln-3 in regulating NK cell activation by studying a patient with kindlin-3 deficiency (leukocyte adhe-sion deficiency-Ill). 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 con-trast, for activation through multiple re-ceptors, kindlln-3 deficiency is overcome and target cells killed. The realization that NK cell activity Is Impaired, but not ab-sent in leukocyte adhesion deficiency, may lead to the development of more efficient therapy for this rare disease. (Blood. 2012;120(19):3915-3924) [ABSTRACT FROM AUTHOR]