title: Immunomodulatory effect of poly-γ-glutamic acid derived from Bacillus subtilis on natural killer dendritic cells.
abstract: Bacillus subtilis-derived poly-γ-glutamic acid (γPGA) stimulates dendritic cells (DCs) to produce IL12, leading to CD4(+) T cell differentiation toward the Th1 phenotype, but DCs consist of heterogeneous subpopulations with a variety of immune functions. Among these, natural killer dendritic cells (NKDCs) play an important role in anti-tumor immune responses. Herein, we demonstrate the role of NKDCs in γPGA-meditated anti-tumor immune responses. NK1.1(+) CD11c(+) NKDCs were stimulated upon γPGA stimulation in vitro and in vivo to up-regulate lymphocyte activation markers, MHC class I and II, and co-stimulatory molecules. In particular, NKDCs were activated by γPGA to produce IFNγ and TNFα, like NK cells, as well as IL12, like DCs, implying that NKDCs have unique and multifunctional roles. Importantly, NKDCs stimulated by γPGA conferred stronger anti-tumor effects in mice and showed increased cytotoxicity against various tumor cell lines in vitro. In conclusion, NKDCs are one of the key players in anti-tumor immunity induced by γPGA.
authors.affiliation: Dept. of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea; School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Dept. of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Park
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea. Electronic address: naykim@amc.seoul.kr.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Dept. of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea. Electronic address: shong@sejong.ac.kr.
authors.forename: Seokmann
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D001412:Bacillus subtilis / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007155:Immunologic Factors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid
keywords: Anti-tumor immunity; IFNγ; IL12; NKDC; TNFα; γPGA