Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation
Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it...
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todo:paper_16643224_v8_nJAN_p_Ziblat2023-10-03T16:29:08Z Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation Ziblat, A. Nuñez, S.Y. Iraolagoitia, X.L.R. Spallanzani, R.G. Torres, N.I. Sierra, J.M. Secchiari, F. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. Dendritic cells IFN-γ Interleukin-18 Interleukin-23 Natural killer cells CD56 antigen gamma interferon interleukin 18 interleukin 23 mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 stress activated protein kinase adaptive immunity antibody dependent cellular cytotoxicity Article cell activation cell death cell proliferation cell selection controlled study cytokine release dendritic cell enzyme linked immunosorbent assay flow cytometry human human cell monocyte natural killer cell natural killer cell mediated cytotoxicity normal human protein expression Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-γ by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-γ production by CD56bright NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-κB, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-γ production by both CD56bright and CD56dim NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell "helper" function was dependent on NK cell-derived IFN-γ. Therefore, our results suggest that IL-23 may trigger NK cell-mediated "helper" effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation. © 2018 Ziblat, Nuñez, Raffo Iraolagoitia, Spallanzani, Torres, Sierra, Secchiari, Domaica, Fuertes and Zwirner. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_16643224_v8_nJAN_p_Ziblat |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Dendritic cells IFN-γ Interleukin-18 Interleukin-23 Natural killer cells CD56 antigen gamma interferon interleukin 18 interleukin 23 mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 stress activated protein kinase adaptive immunity antibody dependent cellular cytotoxicity Article cell activation cell death cell proliferation cell selection controlled study cytokine release dendritic cell enzyme linked immunosorbent assay flow cytometry human human cell monocyte natural killer cell natural killer cell mediated cytotoxicity normal human protein expression |
| spellingShingle |
Dendritic cells IFN-γ Interleukin-18 Interleukin-23 Natural killer cells CD56 antigen gamma interferon interleukin 18 interleukin 23 mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 stress activated protein kinase adaptive immunity antibody dependent cellular cytotoxicity Article cell activation cell death cell proliferation cell selection controlled study cytokine release dendritic cell enzyme linked immunosorbent assay flow cytometry human human cell monocyte natural killer cell natural killer cell mediated cytotoxicity normal human protein expression Ziblat, A. Nuñez, S.Y. Iraolagoitia, X.L.R. Spallanzani, R.G. Torres, N.I. Sierra, J.M. Secchiari, F. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation |
| topic_facet |
Dendritic cells IFN-γ Interleukin-18 Interleukin-23 Natural killer cells CD56 antigen gamma interferon interleukin 18 interleukin 23 mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 stress activated protein kinase adaptive immunity antibody dependent cellular cytotoxicity Article cell activation cell death cell proliferation cell selection controlled study cytokine release dendritic cell enzyme linked immunosorbent assay flow cytometry human human cell monocyte natural killer cell natural killer cell mediated cytotoxicity normal human protein expression |
| description |
Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-γ by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-γ production by CD56bright NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-κB, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-γ production by both CD56bright and CD56dim NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell "helper" function was dependent on NK cell-derived IFN-γ. Therefore, our results suggest that IL-23 may trigger NK cell-mediated "helper" effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation. © 2018 Ziblat, Nuñez, Raffo Iraolagoitia, Spallanzani, Torres, Sierra, Secchiari, Domaica, Fuertes and Zwirner. |
| format |
JOUR |
| author |
Ziblat, A. Nuñez, S.Y. Iraolagoitia, X.L.R. Spallanzani, R.G. Torres, N.I. Sierra, J.M. Secchiari, F. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. |
| author_facet |
Ziblat, A. Nuñez, S.Y. Iraolagoitia, X.L.R. Spallanzani, R.G. Torres, N.I. Sierra, J.M. Secchiari, F. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. |
| author_sort |
Ziblat, A. |
| title |
Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation |
| title_short |
Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation |
| title_full |
Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation |
| title_fullStr |
Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation |
| title_full_unstemmed |
Interleukin (IL)-23 stimulates IFN-γ secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation |
| title_sort |
interleukin (il)-23 stimulates ifn-γ secretion by cd56bright natural killer cells and enhances il-18-driven dendritic cells activation |
| url |
http://hdl.handle.net/20.500.12110/paper_16643224_v8_nJAN_p_Ziblat |
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1807319537802018816 |