Related resources
Full-text held externally
- PMID: 22983444
- UKPMCID: 22983444
- DOI: 10.1182/blood-2012-02-410795
Search for item elsewhere
University researcher(s)
Academic department(s)
Loss of kindlin-3 alters the threshold for NK cell activation in human leukocyte adhesion deficiency-III.
Gruda, Raizy; Brown, Alice C N; Grabovsky, Valentin; Mizrahi, Saar; Gur, Chamutal; Feigelson, Sara W; Achdout, Hagit; Bar-On, Yotam; Alon, Ronen; Aker, Memet; Davis, Daniel M; Mandelboim, Ofer
Blood. 2012;120(19):3915-24.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- PMID: 22983444
- UKPMCID: 22983444
- DOI: 10.1182/blood-2012-02-410795
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.