Oskar Eriksson – Translational studies of the complement system

We are studying the body’s complement system, which is part of the innate immune system. We are interested in the mechanism behind how the complement system is activated in humans, and its role in diseases characterized by systemic inflammation. An important aim of our research is to develop and refine complement diagnostics.

The complement system constitutes one of the branches of the innate immune system and functions as an intravascular surveillance system that serves to purge the vascular system of pathogens and cellular debris.

It accomplishes these tasks by tagging foreign surfaces with powerful opsonins, by generating potent pro-inflammatory mediators at sites of activation, and by directly lysing target cells through cell-surface assembly of the membrane attack complex (MAC). Recently, the discovery of non-canonical intracellular functions of complement factors has opened up a new research direction in the complement field.

Activation via the lectin pathway

We are focusing our efforts on the lectin pathway, one of the three main complement activation pathways and the most recent one to be discovered. The lectin pathway is activated by a series of circulating pattern recognition molecules that trigger complement activation through complex-bound Masp proteases upon target recognition (see figure below).

Most studies of the lectin pathway have focused on mannose-binding lectin (MBL) as this was the first component to be discovered, and constitutes the major lectin pathway initiator in rodents. However, the lectin pathway has undergone considerable evolution after branching of the rodent lineage, and is mainly initiated in humans by ficolin-3, a primate-specific pattern recognition molecule that does not exist in rodents.

Ficolin-3 circulates in plasma in high concentration, but has an unknown function and a poorly defined binding specificity. Hence, the physiological role of ficolin-3 constitutes an important knowledge gap in the complement field that we are aiming to address.

Read more about our projects

Schematic drawing of molecules involved in the lectin pathway.

Overview of complement activation via the lectin pathway. Pattern recognition molecules (MBL, collectins or ficolins) bind to pathogens or damage-associated molecular patterns exposed on cell surfaces to trigger complement activation via associated Masp proteases (yellow). Activation of complement C3 to C3b leads to opsonization, and eventually membrane attack complex (MAC) formation.

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