Biochemical and Biophysical Research Communications 464 (2015) 512-518

 

Activation of human natural killer cells by the soluble

form of cellular prion protein

Yeon-Jae Seong a, b, 1, Pil Soo Sung a, 1, Young-Soon Jang a, Young Joon Choi a,
Bum-Chan Park c, Su-Hyung Park d, Young Woo Park c, Eui-Cheol Shin

 

Abstract

Cellular prion protein (PrPC) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrPC in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrPC protein on human natural killer (NK) cells. Recombinant soluble PrPC protein was generated by fusion of human PrPC with the Fc portion of human IgG1 (PrPC-Fc). PrPC-Fc binds to the surface of human NK cells, particularly to CD56dim NK cells. PrPC-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrPC-Fc facilitated the IL-15-induced proliferation of NK cells. PrPC-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrPC-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrPC-Fc protein activates human NK cells via the ERK and JNK signaling pathways.



Keyword: Cellular prion protein, Natural killer cells Activation, Cytokines