Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses

• Verfasst von: Eberle, Mariel-Esther [VerfasserIn]
• Verfasst von: Dalpke, Alexander [VerfasserIn]
• Titel: Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses
• Verf.angabe: Mariel E. Eberle and Alexander H. Dalpke
• E-Jahr: 2012
• Jahr: 30 April 2012
• Umfang: 11 S.
• Fussnoten: Gesehen am 16.04.219
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2012
• Band/Heft Quelle: 188(2012), 11, Seite 5644-5654
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.1103068
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Animals
• Sach-SW: Bone Marrow Cells
• Sach-SW: Cell Differentiation
• Sach-SW: Cells, Cultured
• Sach-SW: Gene Knockdown Techniques
• Sach-SW: Lectins, C-Type
• Sach-SW: Macrophages
• Sach-SW: Mice
• Sach-SW: Mice, Inbred C57BL
• Sach-SW: Mice, Knockout
• Sach-SW: NF-kappa B
• Sach-SW: Receptor Cross-Talk
• Sach-SW: Signal Transduction
• Sach-SW: Suppressor of Cytokine Signaling 1 Protein
• Sach-SW: Suppressor of Cytokine Signaling Proteins
• Sach-SW: T-Lymphocyte Subsets
• Sach-SW: Toll-Like Receptors
• K10plus-PPN: 1663283702

Abstract

Suppressor of cytokine signaling (SOCS) proteins serve as negative regulators of cytokine receptor signaling. However, SOCS proteins are not only induced via the JAK/STAT pathway, but are also transcribed on triggering of pattern recognition receptors such as TLRs. We now show that SOCS1 can also be induced by the non-TLR pattern recognition receptor Dectin-1 in murine bone marrow-derived dendritic cells and macrophages (BMMs). The C-type lectin Dectin-1 binds to yeasts and signals either in an autonomous manner or can be triggered in combination with TLRs. In our study, SOCS1 was expressed independently of any TLR engagement as a direct target gene of the Dectin-1 ligand Zymosan. Induction of SOCS1 was mediated by a novel pathway encompassing the tyrosine kinases Src and Syk that activated the downstream kinase proline-rich tyrosine kinase 2. Proline-rich tyrosine kinase 2, in turn, caused activation of the MAPK ERK, thereby triggering SOCS1 induction. SOCS1 did not modulate Dectin-1 signaling but affected TLR signaling, leading to decreased and abbreviated NF-κB activation in BMMs triggered by TLR9. Furthermore, IL-12 and IL-10 secretion were inhibited by SOCS1. We additionally observed that IL-17-producing Th cells were clearly increased by SOCS1 in BMMs. Our results show that SOCS1 is expressed via a new, NF-κB-independent pathway in Dectin-1-triggered murine BMMs and influences TLR cross talk and T cell priming.