Interplay of classical and atypical chemokine receptors in immune cell trafficking and dynamic microarchitecture of the secondary lymphoid organs

Atypical chemokine receptors (ACKR), unlike the classic (typical) chemokine receptors, do not trigger cell migration. These receptors rather act as decoy, eliminating or trancytosing chemokines. Research from the recent years has shown that ACKRs play a key role in the regulation of the chemokine system. In this project, the similarities and discrepancies of the function of three atypical receptors (ACKR1, ACKR3 and ACKR4) will be assessed.

The group of atypical chemokine receptors (ACKR1-4) has recently been defined as receptors that are structurally related, although they do not follow the classical scheme of G-protein coupled receptors and do not interact with G-proteins. Nevertheless ACKRs can contribute through their capacity as effective eliminators of chemokines to form gradients. Francis Crick concluded already in the 70s that the persistence of spatial chemoattractant gradients requires the presence of corresponding sinks in juxtaposition to their sources. Such gradients of chemokines are essential for effective innate and adaptive immune responses.

The project aims to demonstrate that gradients of chemokines exist in lymphoid tissue and, with a special focus on the function of ACKR. The consortium expects that the results will bring new insights into the regulation of immune response, which can be important, both in the fight against pathogens and in autoimmunity.