25 June 2014 The balance between adhesion and migration

Increased adhesion of LFA-1 ligands (red spots) on a CCL21-stimulated dendritic cell

Re-activating adhesion on cells of the immune system in Plos One A recent single molecule study carried out by Kyra Borgman, Thomas van Zanten and Carlo Manzo in the Single Molecule Biophotonics group led by ICREA Professor at ICFO Maria Garcia-Parajo sheds new light on the tight balance between cell adhesion and migration in the immune system. The study reveals that integrin receptors (involved in controlling cell adhesion and migration) can be re-activated in mature dendritic cells and that their lateral mobility on the plasma membrane is crucial for avidity regulation impacting on integrin adhesion. This work has been published in Plos One.

Leukocyte integrins are receptors involved in adhesion and migration of cells of the immune system. It has been long believed that on migratory mature dendritic cells (mDCs), the specific leukocyte integrin receptor LFA-1 is inactive. However, recent data suggest that LFA-1 on mDCs may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process had not been addressed yet, despite its crucial importance in adhesion regulation.

Using single particle tracking, ICFO researchers now show that Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Importantly, the data demonstrated that chemokines alone are not sufficient to trigger the high affinity state of LFA-1, but that nanoclustering and mobility are major players in transiently re-activating LFA-1 adhesion. The tight balance between adhesion and migration is crucially important for proper immune response. Failure of this regulation has dramatic health consequences resulting in pathologies such as cancer, autoimmune diseases and chronic inflammation.

This research has been performed in collaboration with a team of scientists from the Radboud University Medical Center in Nijmegen, NL and the Esther Koplowitz Center in Barcelona.