Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j
NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete proinflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become proinflammatory (M1) or anti-inflammatory (M2) cells. Al...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00221767_v200_n3_p1008_Nunez |
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todo:paper_00221767_v200_n3_p1008_Nunez2023-10-03T14:28:02Z Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j Nuñez, S.Y. Ziblat, A. Secchiari, F. Torres, N.I. Sierra, J.M. Raffo Iraolagoitia, X.L. Araya, R.E. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. CD56 antigen gamma interferon HLA G antigen leukocyte antigen leukocyte immunoglobulin like receptor subfamily B member 1 LILRB1 protein, human NCAM1 protein, human transforming growth factor beta cell communication cell culture coculture human immunology lymphocyte activation macrophage macrophage activation metabolism natural killer cell secretion (process) Antigens, CD CD56 Antigen Cell Communication Cells, Cultured Coculture Techniques HLA-G Antigens Humans Interferon-gamma Killer Cells, Natural Leukocyte Immunoglobulin-like Receptor B1 Lymphocyte Activation Macrophage Activation Macrophages Transforming Growth Factor beta NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete proinflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become proinflammatory (M1) or anti-inflammatory (M2) cells. Although the consequences of the cross-talk between M1 and NK cells are known, the outcome of the cross-talk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-g upon coculture with M2. Also, CD56dim NK cells cocultured with M2 displayed lower degranulation and cytotoxic activity than NK cells cocultured with M1. Soluble TGF-b and M2-driven upregulation of CD85j (ILT-2) on NK cells accounted for the diminished IFN-g production by CD56bright NK cells, whereas M2-driven upregulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN-g production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations. Copyright © 2018 by The American Association of Immunologists, Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221767_v200_n3_p1008_Nunez |
| institution |
Universidad de Buenos Aires |
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I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
CD56 antigen gamma interferon HLA G antigen leukocyte antigen leukocyte immunoglobulin like receptor subfamily B member 1 LILRB1 protein, human NCAM1 protein, human transforming growth factor beta cell communication cell culture coculture human immunology lymphocyte activation macrophage macrophage activation metabolism natural killer cell secretion (process) Antigens, CD CD56 Antigen Cell Communication Cells, Cultured Coculture Techniques HLA-G Antigens Humans Interferon-gamma Killer Cells, Natural Leukocyte Immunoglobulin-like Receptor B1 Lymphocyte Activation Macrophage Activation Macrophages Transforming Growth Factor beta |
| spellingShingle |
CD56 antigen gamma interferon HLA G antigen leukocyte antigen leukocyte immunoglobulin like receptor subfamily B member 1 LILRB1 protein, human NCAM1 protein, human transforming growth factor beta cell communication cell culture coculture human immunology lymphocyte activation macrophage macrophage activation metabolism natural killer cell secretion (process) Antigens, CD CD56 Antigen Cell Communication Cells, Cultured Coculture Techniques HLA-G Antigens Humans Interferon-gamma Killer Cells, Natural Leukocyte Immunoglobulin-like Receptor B1 Lymphocyte Activation Macrophage Activation Macrophages Transforming Growth Factor beta Nuñez, S.Y. Ziblat, A. Secchiari, F. Torres, N.I. Sierra, J.M. Raffo Iraolagoitia, X.L. Araya, R.E. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
| topic_facet |
CD56 antigen gamma interferon HLA G antigen leukocyte antigen leukocyte immunoglobulin like receptor subfamily B member 1 LILRB1 protein, human NCAM1 protein, human transforming growth factor beta cell communication cell culture coculture human immunology lymphocyte activation macrophage macrophage activation metabolism natural killer cell secretion (process) Antigens, CD CD56 Antigen Cell Communication Cells, Cultured Coculture Techniques HLA-G Antigens Humans Interferon-gamma Killer Cells, Natural Leukocyte Immunoglobulin-like Receptor B1 Lymphocyte Activation Macrophage Activation Macrophages Transforming Growth Factor beta |
| description |
NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete proinflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become proinflammatory (M1) or anti-inflammatory (M2) cells. Although the consequences of the cross-talk between M1 and NK cells are known, the outcome of the cross-talk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-g upon coculture with M2. Also, CD56dim NK cells cocultured with M2 displayed lower degranulation and cytotoxic activity than NK cells cocultured with M1. Soluble TGF-b and M2-driven upregulation of CD85j (ILT-2) on NK cells accounted for the diminished IFN-g production by CD56bright NK cells, whereas M2-driven upregulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN-g production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations. Copyright © 2018 by The American Association of Immunologists, Inc. |
| format |
JOUR |
| author |
Nuñez, S.Y. Ziblat, A. Secchiari, F. Torres, N.I. Sierra, J.M. Raffo Iraolagoitia, X.L. Araya, R.E. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. |
| author_facet |
Nuñez, S.Y. Ziblat, A. Secchiari, F. Torres, N.I. Sierra, J.M. Raffo Iraolagoitia, X.L. Araya, R.E. Domaica, C.I. Fuertes, M.B. Zwirner, N.W. |
| author_sort |
Nuñez, S.Y. |
| title |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
| title_short |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
| title_full |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
| title_fullStr |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
| title_full_unstemmed |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
| title_sort |
human m2 macrophages limit nk cell effector functions through secretion of tgf-b and engagement of cd85j |
| url |
http://hdl.handle.net/20.500.12110/paper_00221767_v200_n3_p1008_Nunez |
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