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CD200R-mediated suppression of TLR7 signaling

Monday 12 March 2012

Prof.dr Linde Meyaard

Project
The immune system is organized to detect pathogens and clear the infection. This requires robust activation of the immune system, a process that is harmful for the pathogen, but potentially also cause severe damage to the host [1]. Therefore, activation of the immune system is kept under control by inhibitory receptors that dampen or prevent immune activation.

CD200 receptor (CD200R) is an inhibitory receptor that dampens toll like receptor (TLR) 7 initiated transcription by nuclear factor κB (NF-κB) and interferon responsive factor (IRF). The cytosolic domain of CD200R was shown to interact with RasGAP, a signaling-protein that is prerequisite for CD200R-mediated inhibition [2]. Activation of RasGAP results in inactivation of Ras, a signaling molecule involved in many pathways. The aim of the current project is to confirm the involvement of Ras downstream of RasGAP in CD200R signaling. Furthermore, we would like to assess whether CD200R blocks basal Ras-activity, or that CD200R prevents TLR-mediated activation of Ras.

Techniques
Western blot, FACS, ELISA, RNA isolatie, RT-PCR, cell-culture, isolation of monocytes from peripheral blood, siRNA, microscopy

Duration
6 or 9 months

Contact
Linde Meyaard, l.meyaard@umcutrecht.nl
Dr. Kristin Denzer, k.denzer@umcutrecht.nl, 088 75 643 68

References
Science. 2000 Oct 6;290(5489):84-9. Immune inhibitory receptors. Ravetch JV, Lanier LL.

J Immunol. 2009 Oct 15;183(8):4879-86. Essential roles for Dok2 and RasGAP in CD200 receptor-mediated regulation of human myeloid cells. Mihrshahi R, Barclay AN, Brown MH.


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