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

J Immunol. 2013 Mar 15;190(6):2904-12. doi: 10.4049/jimmunol.1201941. Epub 2013 Feb 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Interleukin-21 Receptor alpha Subunit / biosynthesis
  • Interleukin-21 Receptor alpha Subunit / genetics
  • Interleukins / physiology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Macrophages / enzymology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Molecular Targeted Therapy / methods
  • Monocytes / enzymology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Phagocytes / enzymology
  • Phagocytes / immunology*
  • Phagocytes / metabolism
  • Phagocytosis / immunology*
  • Protein-Tyrosine Kinases / metabolism*
  • Syk Kinase
  • Up-Regulation / immunology*


  • IL21R protein, human
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • interleukin-21