Irisin supports integrin-mediated cell adhesion of lymphocytes

Irisin, a myokine released from skeletal muscle, has recently been found to act as a ligand for the integrins alpha V beta 5, alpha V beta 1, and alpha 5 beta 1 expressed on mesenchymal cells, thereby playing an important role in the metabolic remodeling of the bone, skeletal muscle and adipose tissues. Although the immune-modulatory effects of irisin in chronic inflammation have been documented, its interactions with lymphocytic integrins have yet to be elucidated. Here, we show that irisin supports the cell adhesion of human and mouse lymphocytes. Cell adhesion assays using a panel of inhibitory antibodies to integrins have shown that irisin-mediated lymphocyte adhesion involves multiple integrins including not only alpha 4 beta 1 and alpha 5 beta 1, but also leukocyte-specific alpha L beta 2 and alpha 4 beta 7. Importantly, mouse lymphocytic TK-1 cells that lack the expression of beta 1 integrins have exhibited alpha L beta 2- and alpha 4 beta 7-mediated cell adhesion to irisin. Irisin has also been demonstrated to bind to purified recombinant integrin alpha L beta 2 and alpha 4 beta 7 proteins. Thus, irisin represents a novel ligand for integrin alpha L beta 2 and alpha 4 beta 7, capable of supporting lymphocyte cell adhesion independently of beta 1 integrins. These results suggest that irisin may play an important role in regulating lymphocyte adhesion and migration in the inflamed vasculature.