UNIGE document Doctoral Thesis
previous document  unige:76642  next document
add to browser collection

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

Buatois, Vanessa
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.
URN: urn:nbn:ch:unige-766427
Full text
Thesis (4.9 MB) - document accessible for UNIGE members only Limited access to UNIGE
(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

246 hits



Deposited on : 2015-10-28

Export document
Format :
Citation style :