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Marloes Olde Nordkamp

Thursday 5 September 2013

Immune regulation by LAIR proteins

Promotor: Prof. dr. Linde Meyaard
Defence: 5 September 2013

The immune system needs to be strictly regulated in order to function properly. Inhibitory immune receptors play an important role in fine-tuning the immune response. The general assumption is that too much inhibition leads to immune deficiencies and opportunistic infections of pathogens, while to little inhibition leads to an exaggerated immune response, leading to damage to self or autoimmune disorders.

This thesis focuses on the inhibitory receptor LAIR-1 and proteins derived thereof. We show that soluble LAIR-1 and LAIR-2 might be used as biomarkers in inflammatory diseases such as Rheumatoid Arthritis and that soluble LAIR-1 in amniotic fluid may be useful as a novel biomarker for fetal lung maturation. Furthermore, we show binding of proteins which contain collagen like regions to LAIR-1, thereby identifying new ligands and partially explaining the immune regulatory functions of the innate immune protein Surfactant Protein D. Moreover, we have shown that LAIR-2 fusion protein can inhibit the lectin and classical pathway of the complement system, thereby posing it as a novel potential therapy to prevent rejection after organ transplantation or to prevent myocardial damage following reperfusion of coronary arteries.

Taken together, this thesis provides further insight in the regulation of the immune system via inhibitory immune receptors.