title: IL-21 enhances phagocytosis in mononuclear phagocyte cells: identification of spleen tyrosine kinase as a novel molecular target of IL-21.
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 (γc) and IL-21Rα, 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-21Rα 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.
authors: 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.
authors: Francis
authors: F
authors: Vallières
authors: Denis
authors: D
authors: Girard
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000378:metabolism; D053738:Interleukin-21 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D010586:Phagocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000072377:Syk Kinase; D015854:Up-Regulation / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: C508117:IL21R protein, human; D053631:Interleukin Receptor Common gamma Subunit; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D000098546:Interleukin-21