Project

Protease dependent regulation of IL-33 activity in allergic airway inflammation

Duration
01 January 2019 → Ongoing
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Immunology
    • Immunology
    • Immunology
Keywords
airway inflammation
 
Project description

The prevalence of allergies has risen over the last decades. It is evident that the host immune
system and airway mucosal response determine the development of sensitivity or tolerance to
inhaled allergens.
The status of airway mucosa could predetermine the development of severe airway diseases,
including severe asthma and chronic rhinosinusitis with nasal polyps. Current therapies are often
not helpful in patients with severe asthma or recurrent cases of chronic rhinosinusitis with nasal
polyps. The bacterial and viral agents could facilitate allergic sensitization by secreting factors that
alter airway integrity, cause mucosal damage, inducing the activation of cells of the innate immune
system and airway epithelial cells to produce inflammatory mediators, and ultimately leading to
disease exacerbation. We will address the regulation of airway inflammation by a set of bacterial
and host-derived proteases. Proteases are involved in the final step of the regulation of protein
activity. In our preliminary experiments we show that bacterial proteases could facilitate
inflammatory cascade or cause the inactivation of inflammatory cytokines involved in the regulation
of type 2 immune response depending on the inflammatory settings. The major aim of this proposal
is to study the regulatory mechanisms of inflammatory processes initiated by proteases and the
mechanisms limiting protease activation using relevant animal models and human ex vivo nasal
mucosa.