A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation.
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.
Sedlik
Christine
C
Institut National de la Santé et de la Recherche Médicale Unité 520, Institut Curie, Paris, France.
Orbach
Daniel
D
Veron
Philippe
P
Schweighoffer
Edina
E
Colucci
Francesco
F
Gamberale
Romina
R
Ioan-Facsinay
Andrea
A
Verbeek
Sjef
S
Ricciardi-Castagnoli
Paola
P
Bonnerot
Christian
C
Tybulewicz
Victor L J
VL
Di Santo
James
J
Amigorena
Sebastian
S
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
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