PMID- 12517949 OWN - NLM STAT- MEDLINE DCOM- 20030304 LR - 20220129 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 170 IP - 2 DP - 2003 Jan 15 TI - A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation. PG - 846-52 AB - 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. FAU - Sedlik, Christine AU - Sedlik C AD - Institut National de la Sante et de la Recherche Medicale Unite 520, Institut Curie, Paris, France. FAU - Orbach, Daniel AU - Orbach D FAU - Veron, Philippe AU - Veron P FAU - Schweighoffer, Edina AU - Schweighoffer E FAU - Colucci, Francesco AU - Colucci F FAU - Gamberale, Romina AU - Gamberale R FAU - Ioan-Facsinay, Andrea AU - Ioan-Facsinay A FAU - Verbeek, Sjef AU - Verbeek S FAU - Ricciardi-Castagnoli, Paola AU - Ricciardi-Castagnoli P FAU - Bonnerot, Christian AU - Bonnerot C FAU - Tybulewicz, Victor L J AU - Tybulewicz VL FAU - Di Santo, James AU - Di Santo J FAU - Amigorena, Sebastian AU - Amigorena S LA - eng GR - FS/12/4/29254/BHF_/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Cytokines) RN - 0 (Enzyme Precursors) RN - 0 (Il2rg protein, mouse) RN - 0 (Interleukin Receptor Common gamma Subunit) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Receptors, Fc) RN - 0 (Receptors, IgG) RN - 0 (Receptors, Interleukin-7) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.10.2 (Syk protein, mouse) SB - IM MH - Animals MH - Antigen Presentation/*immunology MH - Bone Marrow Cells/enzymology/immunology/metabolism MH - Cell Differentiation/genetics/*immunology MH - Cells, Cultured MH - Cytokines/biosynthesis MH - Dendritic Cells/*cytology/*enzymology/immunology/metabolism MH - Enzyme Precursors/deficiency/genetics/metabolism/*physiology MH - Fetus MH - Interleukin Receptor Common gamma Subunit MH - Intracellular Signaling Peptides and Proteins MH - Liver Transplantation/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Phosphorylation MH - Protein-Tyrosine Kinases/deficiency/genetics/metabolism/*physiology MH - Receptors, Fc/*physiology MH - Receptors, IgG/physiology MH - Receptors, Interleukin-7/deficiency/genetics MH - Signal Transduction/immunology MH - Syk Kinase MH - Transplantation Chimera/genetics/immunology EDAT- 2003/01/09 04:00 MHDA- 2003/03/05 04:00 CRDT- 2003/01/09 04:00 PHST- 2003/01/09 04:00 [pubmed] PHST- 2003/03/05 04:00 [medline] PHST- 2003/01/09 04:00 [entrez] AID - 10.4049/jimmunol.170.2.846 [doi] PST - ppublish SO - J Immunol. 2003 Jan 15;170(2):846-52. doi: 10.4049/jimmunol.170.2.846.