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Human M2 Macrophages Limit NK Cell Effector Functions through Secretion of TGF-β and Engagement of CD85j.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Feb 01; Vol. 200 (3), pp. 1008-1015. Date of Electronic Publication: 2017 Dec 27. - Publication Year :
- 2018
-
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-γ. 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-γ upon coculture with M2. Also, CD56 <superscript>dim</superscript> NK cells cocultured with M2 displayed lower degranulation and cytotoxic activity than NK cells cocultured with M1. Soluble TGF-β and M2-driven upregulation of CD85j (ILT-2) on NK cells accounted for the diminished IFN-γ production by CD56 <superscript>bright</superscript> NK cells, whereas M2-driven upregulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56 <superscript>dim</superscript> 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-γ production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Antigens, CD immunology
CD56 Antigen metabolism
Cells, Cultured
Coculture Techniques
HLA-G Antigens metabolism
Humans
Interferon-gamma immunology
Leukocyte Immunoglobulin-like Receptor B1 immunology
Macrophages immunology
Transforming Growth Factor beta immunology
Cell Communication immunology
Killer Cells, Natural immunology
Lymphocyte Activation immunology
Macrophage Activation immunology
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 200
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 29282306
- Full Text :
- https://doi.org/10.4049/jimmunol.1700737