IL-21 Enhances Phagocytosis in Mononuclear Phagocyte Cells: Identification of Spleen Tyrosine Kinase as a Novel Molecular Target of IL-21

Vallières, Francis et Girard, Denis (2013). IL-21 Enhances Phagocytosis in Mononuclear Phagocyte Cells: Identification of Spleen Tyrosine Kinase as a Novel Molecular Target of IL-21 Journal of Immunology , vol. 190 , nº 6. pp. 2904-12. DOI: 10.4049/jimmunol.1201941.

Prévisualisation

PDF (Pas respect du droit d'auteur, l'éditeur ne nous permet pas de mettre le document PDF mais seulement l'adresse URL qui conduit au PDF du document) - Image de couverture Télécharger (227kB) | Prévisualisation

Résumé

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 (gammac) and IL-21Ralpha, 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-21Ralpha 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.

Type de document:	Article
Mots-clés libres:	-
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	04 avr. 2017 15:06
Dernière modification:	04 avr. 2017 15:11
URI:	https://espace.inrs.ca/id/eprint/2986

Gestion Actions (Identification requise)

Modifier la notice