IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness

IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ pr...

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Autores principales:	Ziblat, Andrea, Domaica, Carolina Inés, Rossi, Lucas Ezequiel, Fuertes, Mercedes Beatriz
Publicado:	2015
Materias:	Cytotoxicity IFN-γ IL-18 IL-27 NK cells CD69 antigen Fas antigen Fas ligand fludarabine gamma interferon glycoprotein gp 130 immunoglobulin enhancer binding protein interleukin 10 interleukin 12 interleukin 15 interleukin 17 interleukin 18 interleukin 2 interleukin 2 receptor alpha interleukin 27 interleukin 4 interleukin 6 Janus kinase 2 mammalian target of rapamycin mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 mitogen activated protein kinase p38 natural cytotoxicity triggering receptor 1 perforin phosphatidylinositol 3 kinase STAT1 protein stress activated protein kinase transcription factor T bet tumor necrosis factor tumor necrosis factor related apoptosis inducing ligand IL27 protein, human IL2RA protein, human IL6ST protein, human interleukin 18 protein, human interleukin derivative lectin leukocyte antigen monoclonal antibody recombinant protein T lymphocyte antigen Article cancer cell line cell maturation cell mediated cytotoxicity cell surface cell viability coculture controlled study cytokine release cytokine response dendritic cell effector cell enzyme linked immunosorbent assay exocytosis flow cytometry HCT116 cell line human human cell lymphocyte function natural killer cell priority journal protein expression protein protein interaction Raji cell line secretory pathway T 47D cell target cell upregulation cell proliferation cell survival cytology cytotoxicity drug effects gene expression regulation genetics immunology primary cell culture signal transduction Antibodies, Monoclonal Antigens, CD Antigens, Differentiation, T-Lymphocyte Cell Proliferation Cell Survival Coculture Techniques Cytokine Receptor gp130 Cytotoxicity, Immunologic Dendritic Cells Gene Expression Regulation HCT116 Cells Humans Interleukin-18 Interleukin-2 Receptor alpha Subunit Interleukins Killer Cells, Natural Lectins, C-Type Primary Cell Culture Recombinant Proteins Signal Transduction
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v45_n1_p192_Ziblat http://hdl.handle.net/20.500.12110/paper_00142980_v45_n1_p192_Ziblat
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00142980_v45_n1_p192_Ziblat
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Cytotoxicity IFN-γ IL-18 IL-27 NK cells CD69 antigen Fas antigen Fas ligand fludarabine gamma interferon glycoprotein gp 130 immunoglobulin enhancer binding protein interleukin 10 interleukin 12 interleukin 15 interleukin 17 interleukin 18 interleukin 2 interleukin 2 receptor alpha interleukin 27 interleukin 4 interleukin 6 Janus kinase 2 mammalian target of rapamycin mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 mitogen activated protein kinase p38 natural cytotoxicity triggering receptor 1 perforin phosphatidylinositol 3 kinase STAT1 protein stress activated protein kinase transcription factor T bet tumor necrosis factor tumor necrosis factor related apoptosis inducing ligand CD69 antigen glycoprotein gp 130 IL27 protein, human IL2RA protein, human IL6ST protein, human interleukin 18 interleukin 18 protein, human interleukin 2 receptor alpha interleukin derivative lectin leukocyte antigen monoclonal antibody recombinant protein T lymphocyte antigen Article cancer cell line cell maturation cell mediated cytotoxicity cell surface cell viability coculture controlled study cytokine release cytokine response dendritic cell effector cell enzyme linked immunosorbent assay exocytosis flow cytometry HCT116 cell line human human cell lymphocyte function natural killer cell priority journal protein expression protein protein interaction Raji cell line secretory pathway T 47D cell target cell upregulation cell proliferation cell survival cytology cytotoxicity drug effects gene expression regulation genetics immunology natural killer cell primary cell culture signal transduction Antibodies, Monoclonal Antigens, CD Antigens, Differentiation, T-Lymphocyte Cell Proliferation Cell Survival Coculture Techniques Cytokine Receptor gp130 Cytotoxicity, Immunologic Dendritic Cells Gene Expression Regulation HCT116 Cells Humans Interleukin-18 Interleukin-2 Receptor alpha Subunit Interleukins Killer Cells, Natural Lectins, C-Type Primary Cell Culture Recombinant Proteins Signal Transduction
spellingShingle	Cytotoxicity IFN-γ IL-18 IL-27 NK cells CD69 antigen Fas antigen Fas ligand fludarabine gamma interferon glycoprotein gp 130 immunoglobulin enhancer binding protein interleukin 10 interleukin 12 interleukin 15 interleukin 17 interleukin 18 interleukin 2 interleukin 2 receptor alpha interleukin 27 interleukin 4 interleukin 6 Janus kinase 2 mammalian target of rapamycin mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 mitogen activated protein kinase p38 natural cytotoxicity triggering receptor 1 perforin phosphatidylinositol 3 kinase STAT1 protein stress activated protein kinase transcription factor T bet tumor necrosis factor tumor necrosis factor related apoptosis inducing ligand CD69 antigen glycoprotein gp 130 IL27 protein, human IL2RA protein, human IL6ST protein, human interleukin 18 interleukin 18 protein, human interleukin 2 receptor alpha interleukin derivative lectin leukocyte antigen monoclonal antibody recombinant protein T lymphocyte antigen Article cancer cell line cell maturation cell mediated cytotoxicity cell surface cell viability coculture controlled study cytokine release cytokine response dendritic cell effector cell enzyme linked immunosorbent assay exocytosis flow cytometry HCT116 cell line human human cell lymphocyte function natural killer cell priority journal protein expression protein protein interaction Raji cell line secretory pathway T 47D cell target cell upregulation cell proliferation cell survival cytology cytotoxicity drug effects gene expression regulation genetics immunology natural killer cell primary cell culture signal transduction Antibodies, Monoclonal Antigens, CD Antigens, Differentiation, T-Lymphocyte Cell Proliferation Cell Survival Coculture Techniques Cytokine Receptor gp130 Cytotoxicity, Immunologic Dendritic Cells Gene Expression Regulation HCT116 Cells Humans Interleukin-18 Interleukin-2 Receptor alpha Subunit Interleukins Killer Cells, Natural Lectins, C-Type Primary Cell Culture Recombinant Proteins Signal Transduction Ziblat, Andrea Domaica, Carolina Inés Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
topic_facet	Cytotoxicity IFN-γ IL-18 IL-27 NK cells CD69 antigen Fas antigen Fas ligand fludarabine gamma interferon glycoprotein gp 130 immunoglobulin enhancer binding protein interleukin 10 interleukin 12 interleukin 15 interleukin 17 interleukin 18 interleukin 2 interleukin 2 receptor alpha interleukin 27 interleukin 4 interleukin 6 Janus kinase 2 mammalian target of rapamycin mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 mitogen activated protein kinase p38 natural cytotoxicity triggering receptor 1 perforin phosphatidylinositol 3 kinase STAT1 protein stress activated protein kinase transcription factor T bet tumor necrosis factor tumor necrosis factor related apoptosis inducing ligand CD69 antigen glycoprotein gp 130 IL27 protein, human IL2RA protein, human IL6ST protein, human interleukin 18 interleukin 18 protein, human interleukin 2 receptor alpha interleukin derivative lectin leukocyte antigen monoclonal antibody recombinant protein T lymphocyte antigen Article cancer cell line cell maturation cell mediated cytotoxicity cell surface cell viability coculture controlled study cytokine release cytokine response dendritic cell effector cell enzyme linked immunosorbent assay exocytosis flow cytometry HCT116 cell line human human cell lymphocyte function natural killer cell priority journal protein expression protein protein interaction Raji cell line secretory pathway T 47D cell target cell upregulation cell proliferation cell survival cytology cytotoxicity drug effects gene expression regulation genetics immunology natural killer cell primary cell culture signal transduction Antibodies, Monoclonal Antigens, CD Antigens, Differentiation, T-Lymphocyte Cell Proliferation Cell Survival Coculture Techniques Cytokine Receptor gp130 Cytotoxicity, Immunologic Dendritic Cells Gene Expression Regulation HCT116 Cells Humans Interleukin-18 Interleukin-2 Receptor alpha Subunit Interleukins Killer Cells, Natural Lectins, C-Type Primary Cell Culture Recombinant Proteins Signal Transduction
description	IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC-NK-cell crosstalk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion, which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK-cell-mediated cytotoxicity against Raji, T-47D, and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent cell-mediated cytotoxicity against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
author	Ziblat, Andrea Domaica, Carolina Inés Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz
author_facet	Ziblat, Andrea Domaica, Carolina Inés Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz
author_sort	Ziblat, Andrea
title	IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_short	IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_full	IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_fullStr	IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_full_unstemmed	IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_sort	il-27 stimulates human nk-cell effector functions and primes nk cells for il-18 responsiveness
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v45_n1_p192_Ziblat http://hdl.handle.net/20.500.12110/paper_00142980_v45_n1_p192_Ziblat
work_keys_str_mv	AT ziblatandrea il27stimulateshumannkcelleffectorfunctionsandprimesnkcellsforil18responsiveness AT domaicacarolinaines il27stimulateshumannkcelleffectorfunctionsandprimesnkcellsforil18responsiveness AT rossilucasezequiel il27stimulateshumannkcelleffectorfunctionsandprimesnkcellsforil18responsiveness AT fuertesmercedesbeatriz il27stimulateshumannkcelleffectorfunctionsandprimesnkcellsforil18responsiveness
_version_	1768542204676014080
spelling	paper:paper_00142980_v45_n1_p192_Ziblat2023-06-08T14:36:48Z IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness Ziblat, Andrea Domaica, Carolina Inés Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz Cytotoxicity IFN-γ IL-18 IL-27 NK cells CD69 antigen Fas antigen Fas ligand fludarabine gamma interferon glycoprotein gp 130 immunoglobulin enhancer binding protein interleukin 10 interleukin 12 interleukin 15 interleukin 17 interleukin 18 interleukin 2 interleukin 2 receptor alpha interleukin 27 interleukin 4 interleukin 6 Janus kinase 2 mammalian target of rapamycin mitogen activated protein kinase kinase 1 mitogen activated protein kinase kinase 2 mitogen activated protein kinase p38 natural cytotoxicity triggering receptor 1 perforin phosphatidylinositol 3 kinase STAT1 protein stress activated protein kinase transcription factor T bet tumor necrosis factor tumor necrosis factor related apoptosis inducing ligand CD69 antigen glycoprotein gp 130 IL27 protein, human IL2RA protein, human IL6ST protein, human interleukin 18 interleukin 18 protein, human interleukin 2 receptor alpha interleukin derivative lectin leukocyte antigen monoclonal antibody recombinant protein T lymphocyte antigen Article cancer cell line cell maturation cell mediated cytotoxicity cell surface cell viability coculture controlled study cytokine release cytokine response dendritic cell effector cell enzyme linked immunosorbent assay exocytosis flow cytometry HCT116 cell line human human cell lymphocyte function natural killer cell priority journal protein expression protein protein interaction Raji cell line secretory pathway T 47D cell target cell upregulation cell proliferation cell survival cytology cytotoxicity drug effects gene expression regulation genetics immunology natural killer cell primary cell culture signal transduction Antibodies, Monoclonal Antigens, CD Antigens, Differentiation, T-Lymphocyte Cell Proliferation Cell Survival Coculture Techniques Cytokine Receptor gp130 Cytotoxicity, Immunologic Dendritic Cells Gene Expression Regulation HCT116 Cells Humans Interleukin-18 Interleukin-2 Receptor alpha Subunit Interleukins Killer Cells, Natural Lectins, C-Type Primary Cell Culture Recombinant Proteins Signal Transduction IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC-NK-cell crosstalk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion, which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK-cell-mediated cytotoxicity against Raji, T-47D, and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent cell-mediated cytotoxicity against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Fil:Ziblat, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Domaica, C.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rossi, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fuertes, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v45_n1_p192_Ziblat http://hdl.handle.net/20.500.12110/paper_00142980_v45_n1_p192_Ziblat

IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness

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