Peripheral blood CD56bright NK cells respond to stem cell factor and adhere to its membrane‐bound form after upregulation of c‐kit. Issue 2 (20th November 2013)

• Record Type: Journal Article
• Authors: Pradier, Amandine; Tabone‐Eglinger, Severine; Huber, Vincent; Bosshard, Carine; Rigal, Emmanuel; Wehrle‐Haller, Bernhard; Roosnek, Eddy
• Is Part Of: European journal of immunology. Volume 44:Issue 2(2014:Feb.)
• Page Start: 511
• Page End: 520
• Publication Date: 2013-11-20
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201343868
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>CD56<sup>bright</sup> NK cells express receptors for IL‐2, IL‐7, IL‐15, and SCF. We found that human peripheral blood CD56<sup>bright</sup> NK cells responded to IL‐2, IL‐7, IL‐15 by phosphorylating STAT‐5, ERK, and Akt but did not respond to SCF. However, CD56<sup>bright</sup> NK cells in culture upregulated c‐kit transcription three to fourfold, which led to a steady increase in c‐kit and a concomitant acquisition of responsiveness to SCF. After 44 h, CD56<sup>bright</sup> NK cells had upregulated c‐kit approximately 20‐fold and phosphorylated ERK and Akt in response to SCF concentrations well below levels present in plasma. CD56<sup>bright</sup> NK cells cultured in IL‐15 maintained c‐kit transcription/expression at ex vivo levels and did not become responsive to SCF. Furthermore, SCF‐responsive, CD56<sup>bright</sup>c‐kit<sup>high</sup> NK cells swiftly downregulated c‐kit and stopped responding to SCF after IL‐15 stimulation. However, commitment of CD56<sup>bright</sup> NK cells to a c‐kit‐negative, SCF‐unresponsive state did not occur, as after 5 days of culture, withdrawal of IL‐15 restored c‐kit to maximal levels and reestablished SCF‐responsiveness. CD56<sup>bright</sup> NK cells that had upregulated c‐kit firmly adhered to COS cells transfected with the membrane form of SCF. Furthermore, SCF signaling significantly increased the capacity of CD56<sup>bright</sup> NK cells to degranulate. Collectively, our data suggest that c‐kit on human CD56<sup>bright</sup> NK cells is a functional receptor that is downregulated in peripheral blood, possibly to render CD56<sup>bright</sup> NK cells unresponsive to the SCF therein.</p> </abstract>