دورية أكاديمية
Human M2 Macrophages Limit NK Cell Effector Functions through Secretion of TGF-β and Engagement of CD85j.
| العنوان: | Human M2 Macrophages Limit NK Cell Effector Functions through Secretion of TGF-β and Engagement of CD85j. |
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| المؤلفون: | Nuñez SY; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Ziblat A; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Secchiari F; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Torres NI; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Sierra JM; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Raffo Iraolagoitia XL; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Araya RE; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Domaica CI; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Fuertes MB; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and., Zwirner NW; Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, C1428ADN Buenos Aires, Argentina; and nzwirner@ibyme.conicet.gov.ar.; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Feb 01; Vol. 200 (3), pp. 1008-1015. Date of Electronic Publication: 2017 Dec 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Cell Communication/*immunology , Killer Cells, Natural/*immunology , Lymphocyte Activation/*immunology , Macrophage Activation/*immunology , Transforming Growth Factor beta/*metabolism, 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 |
| مستخلص: | 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 dim 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 bright NK cells, whereas M2-driven upregulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56 dim 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. (Copyright © 2018 by The American Association of Immunologists, Inc.) |
| المشرفين على المادة: | 0 (Antigens, CD) 0 (CD56 Antigen) 0 (HLA-G Antigens) 0 (LILRB1 protein, human) 0 (Leukocyte Immunoglobulin-like Receptor B1) 0 (NCAM1 protein, human) 0 (Transforming Growth Factor beta) 82115-62-6 (Interferon-gamma) |
| تواريخ الأحداث: | Date Created: 20171229 Date Completed: 20181001 Latest Revision: 20181202 |
| رمز التحديث: | 20231215 |
| DOI: | 10.4049/jimmunol.1700737 |
| PMID: | 29282306 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.1700737 |