TY - JOUR
T1 - Immunomodulatory effect of poly-γ-glutamic acid derived from Bacillus subtilis on natural killer dendritic cells
AU - Lee, Sung Won
AU - Park, Hyun Jung
AU - Park, Se Ho
AU - Kim, Nayoung
AU - Hong, Seokmann
PY - 2014/1/10
Y1 - 2014/1/10
N2 - 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.
AB - 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.
KW - Anti-tumor immunity
KW - IFNγ
KW - IL12
KW - NKDC
KW - TNFα
KW - γPGA
UR - http://www.scopus.com/inward/record.url?scp=84892441982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892441982&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2013.11.097
DO - 10.1016/j.bbrc.2013.11.097
M3 - Article
C2 - 24309101
AN - SCOPUS:84892441982
VL - 443
SP - 413
EP - 421
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -