title: Activation of human natural killer cells by the soluble form of cellular prion protein.
abstract: Cellular prion protein (PrP(C)) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP(C) in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP(C) protein on human natural killer (NK) cells. Recombinant soluble PrP(C) protein was generated by fusion of human PrP(C) with the Fc portion of human IgG1 (PrP(C)-Fc). PrP(C)-Fc binds to the surface of human NK cells, particularly to CD56(dim) NK cells. PrP(C)-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP(C)-Fc facilitated the IL-15-induced proliferation of NK cells. PrP(C)-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP(C)-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP(C)-Fc protein activates human NK cells via the ERK and JNK signaling pathways.
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea; Hafis Clinic, Seoul, Republic of Korea.
authors.forename: Yeon-Jae
authors.initials: YJ
authors.lastname: Seong
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Pil Soo
authors.initials: PS
authors.lastname: Sung
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Jang
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Bum-Chan
authors.initials: BC
authors.lastname: Park
authors.affiliation: Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Su-Hyung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Park
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea. Electronic address: ecshin@kaist.ac.kr.
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
mesh_terms: D015550:Cell Degranulation / Q000502:physiology; D002478:Cells, Cultured; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018621:PrPC Proteins / Q000502:physiology*
chemical_list: D018621:PrPC Proteins; D048670:MAP Kinase Kinase 4; D053804:Granzymes
keywords: Activation; Cellular prion protein; Cytokines; Natural killer cells