Artículo

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" (2018) Journal of Immunology. 200(3):1008-1015
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Abstract:

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.

Registro:

Documento: Artículo
Título:Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j
Autor: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.
Filiación:Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, Buenos Aires, C1428ADN, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Cancer Research UK Beatson Institute, Bearsden, Glasgow, United Kingdom
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina
Palabras clave: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
Año:2018
Volumen:200
Número:3
Página de inicio:1008
Página de fin:1015
DOI: http://dx.doi.org/10.4049/jimmunol.1700737
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:gamma interferon, 82115-62-6; Antigens, CD; CD56 Antigen; HLA-G Antigens; Interferon-gamma; Leukocyte Immunoglobulin-like Receptor B1; LILRB1 protein, human; NCAM1 protein, human; Transforming Growth Factor beta
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v200_n3_p1008_Nunez

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Citas:

---------- APA ----------
Nuñez, S.Y., Ziblat, A., Secchiari, F., Torres, N.I., Sierra, J.M., Raffo Iraolagoitia, X.L., Araya, R.E.,..., Zwirner, N.W. (2018) . Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j. Journal of Immunology, 200(3), 1008-1015.
http://dx.doi.org/10.4049/jimmunol.1700737
---------- CHICAGO ----------
Nuñez, S.Y., Ziblat, A., Secchiari, F., Torres, N.I., Sierra, J.M., Raffo Iraolagoitia, X.L., et al. "Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j" . Journal of Immunology 200, no. 3 (2018) : 1008-1015.
http://dx.doi.org/10.4049/jimmunol.1700737
---------- MLA ----------
Nuñez, S.Y., Ziblat, A., Secchiari, F., Torres, N.I., Sierra, J.M., Raffo Iraolagoitia, X.L., et al. "Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j" . Journal of Immunology, vol. 200, no. 3, 2018, pp. 1008-1015.
http://dx.doi.org/10.4049/jimmunol.1700737
---------- VANCOUVER ----------
Nuñez, S.Y., Ziblat, A., Secchiari, F., Torres, N.I., Sierra, J.M., Raffo Iraolagoitia, X.L., et al. Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j. J. Immunol. 2018;200(3):1008-1015.
http://dx.doi.org/10.4049/jimmunol.1700737