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

Diplôme Thèse Modulation of the assembly of the IL-6 signaling complex and its biological consequences eng 2015-09-03 author Lacroix Marine 755255 director Gruenberg Jean 29661 director Buatois Vanessa 10.13097/archive-ouverte/unige:76642 urn:nbn:ch:unige-766427 Sc. 4819 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. Dewey 540 28 Section de chimie et biochimie 14 false aeb55007-4a02-46d0-928c-f6dc4ef835db Thesis Restricted Thesis_Lacroix.pdf 5123693 application/pdf Private 2016-10-04 0075925379feb8b81bf24ab83987f3b74c90368adc810fb9d84105350bb067e1 restrictedAccess Faculté des sciences / Section de chimie et biochimie

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Modulation of the assembly of the IL-6 signaling complex and its biological consequences				2015	943	5

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Lacroix, Marine