Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
Cross-talk between mature dendritic cells (mDC) and NK cells through the cell surface receptors NKp30 and DNAM-1 leads to their reciprocal activation. However, the impact of regulatory dendritic cells (regDC) on NK cell function remains unknown. As regDC constrain the immune response in different ph...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v195_n5_p2141_Spallanzani http://hdl.handle.net/20.500.12110/paper_00221767_v195_n5_p2141_Spallanzani |
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paper:paper_00221767_v195_n5_p2141_Spallanzani2023-06-08T14:46:58Z Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors Ziblat, Andrea Rossi, Lucas Ezequiel Domaica, Carolina Inés Fuertes, Mercedes Beatriz CD69 antigen colecalciferol dexamethasone gamma interferon interleukin 10 interleukin 12 interleukin 15 interleukin 18 interleukin 2 receptor alpha lipopolysaccharide major histocompatibility antigen class 1 natural cytotoxicity triggering receptor 1 colecalciferol dexamethasone gamma interferon glucocorticoid HLA antigen class 1 interleukin 10 interleukin 12 interleukin 18 lipopolysaccharide natural cytotoxicity triggering receptor 1 T lymphocyte receptor vitamin apoptosis Article cell function cell interaction controlled study cytokine production cytokine release dendritic cell human human cell lymphocyte function natural killer cell priority journal upregulation biosynthesis cell communication cell culture dendritic cell drug effects flow cytometry immunology metabolism secretion (process) signal transduction Cell Communication Cells, Cultured Cholecalciferol Costimulatory and Inhibitory T-Cell Receptors Dendritic Cells Dexamethasone Flow Cytometry Glucocorticoids Histocompatibility Antigens Class I Humans Interferon-gamma Interleukin-10 Interleukin-12 Interleukin-18 Killer Cells, Natural Lipopolysaccharides Natural Cytotoxicity Triggering Receptor 1 Receptor Cross-Talk Vitamins Cross-talk between mature dendritic cells (mDC) and NK cells through the cell surface receptors NKp30 and DNAM-1 leads to their reciprocal activation. However, the impact of regulatory dendritic cells (regDC) on NK cell function remains unknown. As regDC constrain the immune response in different physiological and pathological conditions, the aim of this work was to investigate the functional outcome of the interaction between regDC and NK cells and the associated underlying mechanisms. RegDC generated from monocyte-derived DC treated either with LPS and dexamethasone, vitamin D3, or vitamin D3 and dexamethasone instructed NK cells to secrete lower amounts of IFN-γ than NK cells exposed to mDC. Although regDC triggered upregulation of the activation markers CD69 and CD25 on NK cells, they did not induce upregulation of CD56 as mDC, and silenced IFN-γ secretion through mechanisms involving insufficient secretion of IL-18, but not IL-12 or IL-15 and/or induction of NK cell apoptosis. Blocking experiments demonstrated that regDC curb IFN-γ secretion by NK cells through a dominant suppressive mechanism involving IL-10, NK cell inhibitory receptors, and, unexpectedly, engagement of the activating receptor NKp46. Our findings unveil a previously unrecognized cross-talk through which regDC shape NK cell function toward an alternative activated phenotype unable to secrete IFN-γ, highlighting the plasticity of NK cells in response to tolerogenic stimuli. In addition, our findings contribute to identify a novel inhibitory role for NKp46 in the control of NK cell function, and have broad implications in the resolution of inflammatory responses and evasion of antitumor responses. Copyright © 2015 by The American Association of Immunologists, Inc. Fil:Ziblat, A. 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:Domaica, C.I. 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_00221767_v195_n5_p2141_Spallanzani http://hdl.handle.net/20.500.12110/paper_00221767_v195_n5_p2141_Spallanzani |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
CD69 antigen colecalciferol dexamethasone gamma interferon interleukin 10 interleukin 12 interleukin 15 interleukin 18 interleukin 2 receptor alpha lipopolysaccharide major histocompatibility antigen class 1 natural cytotoxicity triggering receptor 1 colecalciferol dexamethasone gamma interferon glucocorticoid HLA antigen class 1 interleukin 10 interleukin 12 interleukin 18 lipopolysaccharide natural cytotoxicity triggering receptor 1 T lymphocyte receptor vitamin apoptosis Article cell function cell interaction controlled study cytokine production cytokine release dendritic cell human human cell lymphocyte function natural killer cell priority journal upregulation biosynthesis cell communication cell culture dendritic cell drug effects flow cytometry immunology metabolism secretion (process) signal transduction Cell Communication Cells, Cultured Cholecalciferol Costimulatory and Inhibitory T-Cell Receptors Dendritic Cells Dexamethasone Flow Cytometry Glucocorticoids Histocompatibility Antigens Class I Humans Interferon-gamma Interleukin-10 Interleukin-12 Interleukin-18 Killer Cells, Natural Lipopolysaccharides Natural Cytotoxicity Triggering Receptor 1 Receptor Cross-Talk Vitamins |
| spellingShingle |
CD69 antigen colecalciferol dexamethasone gamma interferon interleukin 10 interleukin 12 interleukin 15 interleukin 18 interleukin 2 receptor alpha lipopolysaccharide major histocompatibility antigen class 1 natural cytotoxicity triggering receptor 1 colecalciferol dexamethasone gamma interferon glucocorticoid HLA antigen class 1 interleukin 10 interleukin 12 interleukin 18 lipopolysaccharide natural cytotoxicity triggering receptor 1 T lymphocyte receptor vitamin apoptosis Article cell function cell interaction controlled study cytokine production cytokine release dendritic cell human human cell lymphocyte function natural killer cell priority journal upregulation biosynthesis cell communication cell culture dendritic cell drug effects flow cytometry immunology metabolism secretion (process) signal transduction Cell Communication Cells, Cultured Cholecalciferol Costimulatory and Inhibitory T-Cell Receptors Dendritic Cells Dexamethasone Flow Cytometry Glucocorticoids Histocompatibility Antigens Class I Humans Interferon-gamma Interleukin-10 Interleukin-12 Interleukin-18 Killer Cells, Natural Lipopolysaccharides Natural Cytotoxicity Triggering Receptor 1 Receptor Cross-Talk Vitamins Ziblat, Andrea Rossi, Lucas Ezequiel Domaica, Carolina Inés Fuertes, Mercedes Beatriz Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
| topic_facet |
CD69 antigen colecalciferol dexamethasone gamma interferon interleukin 10 interleukin 12 interleukin 15 interleukin 18 interleukin 2 receptor alpha lipopolysaccharide major histocompatibility antigen class 1 natural cytotoxicity triggering receptor 1 colecalciferol dexamethasone gamma interferon glucocorticoid HLA antigen class 1 interleukin 10 interleukin 12 interleukin 18 lipopolysaccharide natural cytotoxicity triggering receptor 1 T lymphocyte receptor vitamin apoptosis Article cell function cell interaction controlled study cytokine production cytokine release dendritic cell human human cell lymphocyte function natural killer cell priority journal upregulation biosynthesis cell communication cell culture dendritic cell drug effects flow cytometry immunology metabolism secretion (process) signal transduction Cell Communication Cells, Cultured Cholecalciferol Costimulatory and Inhibitory T-Cell Receptors Dendritic Cells Dexamethasone Flow Cytometry Glucocorticoids Histocompatibility Antigens Class I Humans Interferon-gamma Interleukin-10 Interleukin-12 Interleukin-18 Killer Cells, Natural Lipopolysaccharides Natural Cytotoxicity Triggering Receptor 1 Receptor Cross-Talk Vitamins |
| description |
Cross-talk between mature dendritic cells (mDC) and NK cells through the cell surface receptors NKp30 and DNAM-1 leads to their reciprocal activation. However, the impact of regulatory dendritic cells (regDC) on NK cell function remains unknown. As regDC constrain the immune response in different physiological and pathological conditions, the aim of this work was to investigate the functional outcome of the interaction between regDC and NK cells and the associated underlying mechanisms. RegDC generated from monocyte-derived DC treated either with LPS and dexamethasone, vitamin D3, or vitamin D3 and dexamethasone instructed NK cells to secrete lower amounts of IFN-γ than NK cells exposed to mDC. Although regDC triggered upregulation of the activation markers CD69 and CD25 on NK cells, they did not induce upregulation of CD56 as mDC, and silenced IFN-γ secretion through mechanisms involving insufficient secretion of IL-18, but not IL-12 or IL-15 and/or induction of NK cell apoptosis. Blocking experiments demonstrated that regDC curb IFN-γ secretion by NK cells through a dominant suppressive mechanism involving IL-10, NK cell inhibitory receptors, and, unexpectedly, engagement of the activating receptor NKp46. Our findings unveil a previously unrecognized cross-talk through which regDC shape NK cell function toward an alternative activated phenotype unable to secrete IFN-γ, highlighting the plasticity of NK cells in response to tolerogenic stimuli. In addition, our findings contribute to identify a novel inhibitory role for NKp46 in the control of NK cell function, and have broad implications in the resolution of inflammatory responses and evasion of antitumor responses. Copyright © 2015 by The American Association of Immunologists, Inc. |
| author |
Ziblat, Andrea Rossi, Lucas Ezequiel Domaica, Carolina Inés Fuertes, Mercedes Beatriz |
| author_facet |
Ziblat, Andrea Rossi, Lucas Ezequiel Domaica, Carolina Inés Fuertes, Mercedes Beatriz |
| author_sort |
Ziblat, Andrea |
| title |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
| title_short |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
| title_full |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
| title_fullStr |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
| title_full_unstemmed |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
| title_sort |
regulatory dendritic cells restrain nk cell ifn-γ production through mechanisms involving nkp46, il-10, and mhc class i-specific inhibitory receptors |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v195_n5_p2141_Spallanzani http://hdl.handle.net/20.500.12110/paper_00221767_v195_n5_p2141_Spallanzani |
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| _version_ |
1768545405077815296 |