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Defining the role of autophagy in regulatory T cell function: towards novel strategies to treat autoimmune diseases.


Autophagy is een proces dat wordt aangezet als er onvoldoende voedingsstoffen zijn en is belangrijk voor verschillende cellulaire functies. De onderzoekers hebben bestudeerd
hoe dit proces het afweersysteem kan beïnvloeden. Als we dit beter begrijpen, zou autophagy manipulatie kunnen kunnen helpen bij het bestrijden van autoimmuunziektes
als (jeugd)reuma.


Samenvatting van de aanvraag

Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are common autoimmune diseases with a combined incidence of more than 1% of the population. The current treatment of RA and JIA is insufficient since not all patients respond to treatment and although symptoms are suppressed in responders, the disease is not cured. Regulatory T (Treg) cells are potent immune suppressors, and are therefore key modulators of immune balance. Improving Treg function could thus benefit RA and JIA patients, but how Treg cell function can be improved is still poorly understood. I have recently gathered substantial circumstantial evidence that autophagy is required for Treg cell function. Autophagy is a highly conserved catabolic process that is crucial for the maintenance of cellular homeostasis. Here double-membrane vesicles are formed containing unwanted cytoplasmic proteins and organelles, which are subsequently fused with lysosomes for degradation of their content. Although the role of autophagy in innate immunity is gaining clarity, its role in adaptive immunity remains unclear. The main objective of this project is to obtain a better understanding of the role of autophagy in the regulation of Treg cell function. I furthermore aim to identify autophagy inducing cytokines in the joints of JIA and RA patients. In addition, a screen will be performed to find novel compounds that can manipulate autophagy. To this end, I will use a multidisciplinary translational approach combining unique mouse models with state-of-the-art techniques in immunology, microscopy, and cell biology. Together, these experiments will increase our understanding for the role of autophagy in immune homeostasis and could provide novel strategies to resolve autoimmune diseases including RA and JIA.



Looptijd: 100%
Looptijd: 100 %
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. J. van Loosdregt
Verantwoordelijke organisatie:
Universitair Medisch Centrum Utrecht