Structure-function studies on Interleukin-26, a pro-inflammatory and antimicrobial cytokine.

01 January 2017 → 31 December 2021
Research Foundation - Flanders (FWO)
Research disciplines
No data available
cytokine-receptor interactions Inflammation and immunity antagonist design
Project description

Mammalian cellular development crucially depends on the ability of cytokines, to activate their
cognate receptors at the cell-surface with high specificity in order to establish appropriate
intracellular signalling. The downside of such a key physiological activity is that native and mutant
forms of cytokines and their receptors have been implicated in inflammatory disorders, cellular
malignancies and cancer. In this context, interleukin-26 (IL-26), a pro-inflammatory TH17 cellderived
cytokine, is implicated in the pathology of chronic inflammatory diseases including
rheumatoid arthritis, Crohn’s disease, human lymphatic filariasis, psoriasis and multiple sclerosis.
Remarkably, IL-26 also functions as an antimicrobial agent by lysing bacteria through disturbing
their membrane integrity. The proposed research project aims to provide a timely and detailed
structural, biochemical, biophysical and mechanistic framework for understanding the principles
underlying the assembly of cell-surface receptor signalling complexes and anti-microbial effects
mediated by IL-26. In addition, we will probe the antagonistic potential of an IL-26 trap, in the
context of a fusion protein comprising the extracellular domains of the two IL-26 cognate