De rol van het endoplasmatisch Retriculum Stress in dendritische cellen en immuun-gemedieerde long disesases

01-12-2010 → 30-11-2015
Europese middelen: kaderprogramma
  • Medical and health sciences
    • Respiratory medicine
    • Respiratory medicine
    • Respiratory medicine
endoplasmatisch reticulum endogenous danger signal unfolded protein response

Dendritic cells play crucial roles in the regulation of immunity and in the pathogenesis of many inflammatory lung diseases. These cells react to exogenous and endogenous danger signals. Lung cells of mice and patients exposed to environmental triggers of lung disease like allergens, cigarette smoke, fine dust particles or microbes often accumulate unfolded proteins in the endoplasmic reticulum (ER), leading to an adaptive unfolded protein response (UPR) or to signs of ER stress. Recently, it has been shown that DC’s express transcription factors involved in the UPR. Based on premliminary experiments and on my interpretation of the state – of –the art in the cell biology of ER stress and lung biology, I hypothesize that the presence of unfolded proteins in the ER is a crucial endogenous danger signal that is vital to understanding the biology of lung DCs and their involvement in inflammatory lung diseases. This knowledge on how ER stress regulates DC function could be employed for the development of new drugs for inflammatory lung diseases.