NDLI: IL-21 enhances phagocytosis in mononuclear phagocyte cells: identification of spleen tyrosine kinase as a novel molecular target of IL-21.

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IL-21 enhances phagocytosis in mononuclear phagocyte cells: identification of spleen tyrosine kinase as a novel molecular target of IL-21.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Vallières, Francis Girard, Denis
Description	Country affiliation: Canada Author Affiliation: Vallières F ( Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Québec H7V 1B7, Canada.)
Abstract	The biological significance of the IL-21/IL-21R system in human monocytes/macrophages is not well documented, and the expression of IL-21R is unclear and has been disputed. In this study, we showed for the first time, to our knowledge, that human monocyte-like THP-1 cells expressed the two IL-21R components, CD132 (Î³c) and IL-21R , on their cell surface, as assessed by flow cytometry. Moreover, IL-21 was found to enhance FcR-mediated phagocytosis, but not endocytosis. The ability of IL-21 to enhance phagocytosis was not associated with an increased expression of both IL-21R components at the cell surface, and IL-21 did not act in synergy with IL-15. IL-21 activated spleen tyrosine kinase (Syk), as evidenced by its ability to increase Syk phosphorylation. Using a pharmacological approach to inhibit Syk activity, and an antisense technique to downregulate Syk protein expression, we demonstrated the importance of Syk in IL-21-induced phagocytosis. In addition, both CD132 and IL-21R were expressed on the cell surface of naive monocytes, as well as in GM-CSF-monocyte-derived macrophages. Moreover, IL-21 also induced phagocytosis in these cells. We conclude that IL-21 possesses important biological effects in mononuclear phagocyte cells and that Syk is a novel molecular target of IL-21 that was previously unknown. Therefore, future development of therapeutic strategies targeting the IL-21/IL-21R system should consider that monocyte and macrophage cell physiology may be affected by this system.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-03-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Interleukins Physiology Intracellular Signaling Peptides And Proteins Metabolism Phagocytes Immunology Phagocytosis Protein-tyrosine Kinases Up-regulation Cell Line, Tumor Interleukin Receptor Common Gamma Subunit Interleukin-21 Receptor Alpha Subunit Biosynthesis Genetics Macrophages Enzymology Molecular Targeted Therapy Monocytes Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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