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Titles listModulation of the assembly of the IL-6 signaling complex and its biological consequences
Titles listModulation of the assembly of the IL-6 signaling complex and its biological consequences
Doctoral Thesis
unige:76642 
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Modulation of the assembly of the IL-6 signaling complex and its biological consequences |
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| Defense | Thèse de doctorat : Univ. Genève, 2015 - Sc. 4819 - 2015/09/03 | |
| Abstract | Biological consequences of IL-6 cis- and trans-signaling are described to be homeostatic and pro-inflammatory, respectively. The IL-6R signaling complex has been postulated to be a hexamer identical for inducing both signaling pathways and driven by three distinct sites of interaction. Our aim was to investigate whether the modulation of IL-6 signaling pathways and complex assembly using monoclonal antibodies might translate in vivo and highlight improved IL-6R-targeted therapies. Our data revealed that 1)IL-6 cis- and trans-signaling complexes assemble differently in mouse; 2)this difference highlighted in mouse is not transposable to human; 3)differentially targeting the sites of interaction within the signaling complex results in distinct neutralizing consequences; 4)some physiological effects thought to be mediated by cis-signaling might also be driven by trans-signaling in established inflammation. Finally, anti-IL-6R antibodies with distinct mechanisms of action should allow targeting the inflammatory component of IL-6 while permitting physiological functions to persist in different disease settings. | |
| Identifiers | URN: urn:nbn:ch:unige-766427 | |
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| Citation (ISO format) | LACROIX, Marine. Modulation of the assembly of the IL-6 signaling complex and its biological consequences. Université de Genève. Thèse, 2015. https://archive-ouverte.unige.ch/unige:76642 |
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