title: A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation.
abstract: Dendritic cells (DCs) are the only APCs capable of initiating adaptive immune responses. The initiation of immune responses requires that DCs 1) internalize and present Ags; and 2) undergo a differentiation process, called "maturation", which transforms DCs into efficient APCs. DC maturation may be initiated by the engagement of different surface receptors, including certain cytokine receptors (such as TNFR), Toll-like receptors, CD40, and FcRs. The early activation events that link receptor engagement and DC maturation are not well characterized. We found that FcR engagement by immune complexes induced the phosphorylation of Syk, a protein tyrosine kinase acting immediately downstream of FcRs. Syk was dispensable for DC differentiation in vitro and in vivo, but was strictly required for immune complexes internalization and subsequent Ag presentation to T lymphocytes. Importantly, Syk was also required for the induction of DC maturation and IL-12 production after FcR engagement, but not after engagement of other surface receptors, such as TNFR or Toll-like receptors. Therefore, protein tyrosine phosphorylation by Syk represents a novel pathway for the induction of DC maturation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 520, Institut Curie, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Sedlik
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Philippe
authors.initials: P
authors.lastname: Veron
authors.forename: Edina
authors.initials: E
authors.lastname: Schweighoffer
authors.forename: Francesco
authors.initials: F
authors.lastname: Colucci
authors.forename: Romina
authors.initials: R
authors.lastname: Gamberale
authors.forename: Andrea
authors.initials: A
authors.lastname: Ioan-Facsinay
authors.forename: Sjef
authors.initials: S
authors.lastname: Verbeek
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
authors.forename: Christian
authors.initials: C
authors.lastname: Bonnerot
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: James
authors.initials: J
authors.lastname: Di Santo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D004792:Enzyme Precursors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005333:Fetus; D053631:Interleukin Receptor Common gamma Subunit; D047908:Intracellular Signaling Peptides and Proteins; D016031:Liver Transplantation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D004792:Enzyme Precursors; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D047908:Intracellular Signaling Peptides and Proteins; D011961:Receptors, Fc; D017452:Receptors, IgG; D020395:Receptors, Interleukin-7; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse