Doctoral thesis
English

Modulation of the assembly of the IL-6 signaling complex and its biological consequences

ContributorsLacroix, Marine
Defense date2015-09-03
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.

Citation (ISO format)
LACROIX, Marine. Modulation of the assembly of the IL-6 signaling complex and its biological consequences. Doctoral Thesis, 2015. doi: 10.13097/archive-ouverte/unige:76642
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Creation04/10/2015 16:14:00
First validation04/10/2015 16:14:00
Update time14/03/2023 23:46:03
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