Siglec-E Is Up-Regulated and Phosphorylated Following Lipopolysaccharide Stimulation in Order to Limit TLR-Driven Cytokine Production
| Autor: | Caroline R, Boyd, Selinda J, Orr, Shaun, Spence, James F, Burrows, Joanne, Elliott, Helen P, Carroll, Kiva, Brennan, Joan, Ní Gabhann, Wilson A, Coulter, Claire, Jones, Paul R, Crocker, James A, Johnston, Caroline A, Jefferies |
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| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide medicine.medical_treatment Immunology Down-Regulation Protein Tyrosine Phosphatase Non-Receptor Type 11 Stimulation Sialic acid binding Protein tyrosine phosphatase Biology Article Cell Line Mice chemistry.chemical_compound Antigens CD medicine Animals Humans Immunology and Allergy Phosphorylation Cell Line Transformed Mice Knockout Toll-Like Receptors NF-kappa B SIGLEC respiratory system Up-Regulation Cell biology Antigens Differentiation B-Lymphocyte Mice Inbred C57BL Adaptor Proteins Vesicular Transport Cytokine chemistry TRIF Myeloid Differentiation Factor 88 Cytokines Signal Transduction |
| Zdroj: | The Journal of Immunology. 183:7703-7709 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0902780 |
| Popis: | Although production of cytokines by TLR is essential for viral and bacterial clearance, overproduction can be detrimental, thus controlling these responses is essential. CD33-related sialic acid binding Ig-like lectin receptors (Siglecs) have been implicated in the control of leukocyte responses. In this study, we report that murine Siglec-E is induced by TLRs in a MyD88-specific manner, is tyrosine phosphorylated following LPS stimulation, and negatively regulates TLR responses. Specifically, we demonstrate the Siglec-E expression inhibits TLR-induced NF-κB and more importantly, the induction of the antiviral cytokines IFN-β and RANTES. Siglec-E mediates its inhibitory effects on TIR domain containing adaptor inducing IFN-β (TRIF)-dependent cytokine production via recruitment of the serine/threonine phosphatase SHP2 and subsequent inhibition of TBK1 activity as evidenced by enhanced TBK1 phosphorylation in cells following knockdown of Siglec-E expression. Taken together, our results demonstrate a novel role for Siglec-E in controlling the antiviral response to TLRs and thus helping to maintain a healthy cytokine balance following infection. |
| Databáze: | OpenAIRE |
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