Irisin supports integrin-mediated cell adhesion of lymphocytes

Abstract

Irisin, a myokine released from skeletal muscle, has recently been found to act as a ligand for the integrins αVβ5, αVβ1, and α5β1 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 α4β1 and α5β1, but also leukocyte-specific αLβ2 and α4β7. Importantly, mouse lymphocytic TK-1 cells that lack the expression of β1 integrins have exhibited αLβ2- and α4β7-mediated cell adhesion to irisin. Irisin has also been demonstrated to bind to purified recombinant integrin αLβ2 and α4β7 proteins. Thus, irisin represents a novel ligand for integrin αLβ2 and α4β7, capable of supporting lymphocyte cell adhesion independently of β1 integrins. These results suggest that irisin may play an important role in regulating lymphocyte adhesion and migration in the inflamed vasculature.

Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D

“…Integrins affect an array of signal transduction cascades which mediate cell survival, proliferation, differentiation and organ development 49 . It is also noteworthy that irisin was recently identified as a ligand for the integrins αVβ5, αVβ1, and α5β1 expressed on mesenchymal cells 50,51 . Rho‐family GTPases are of critical importance in integrating intracellular signals downstream of mechano‐sensors, hence promoting re‐organization of the actin cytoskeleton which is necessary for cell‐shape alterations and eventually migration 52 .…”

“…49 It is also noteworthy that irisin was recently identified as a ligand for the integrins αVβ5, αVβ1, and α5β1 expressed on mesenchymal cells. 50,51 Rho-family GTPases are of critical importance in integrating intracellular signals downstream of mechano-sensors, hence promoting re-organization of the actin cytoskeleton which is necessary for cell-shape alterations and eventually migration. 52 Valine is one of the branched-chain amino acids that is needed to synthesize proteins, it can enhance mammary cell growth.…”

Effect of irisin on the epilepsy induced by penicillin G: An electrophysiological study

“…Inflammation control may provide new strategies to treat seizures and epilepsy (47). In addition to its anti-inflammatory properties (26)(27)(28)(29)(30), irisin has protective effects against hypoxia, oxidative stress and apoptosis (48,49). When it is also considered that inflammation promotes the occurrence of epilepsy (50), irisin level may be increased as a protective mechanism against seizure-induced neuroinflammation (24).…”

“…Inflammation in the brain is known to increase neuronal hyperexcitability and seizures (25). With many recent studies, it has been determined that irisin has an anti-inflammatory effect (26)(27)(28)(29)(30). It has been demonstrated that the treatment of irisin reduces inflammation (30) and modulates macrophage activity by reducing the overproduction of reactive oxygen species (ROS) (29).…”

Conserved and convergent mechanisms underlying performance–life-history trade-offs

“…Alterations in myokine signaling have consequently been linked to a variety of human diseases, including diabetes mellitus, heart failure, cancer and chronic obstructive pulmonary disease, as well as aging (Piccirillo, 2019). Although the metabolic effects of myokines have clear links to allocation and availability of energy (Pedersen et al, 2007), there is also evidence that aspects of the immune system, including lymphocyte numbers and activity, can be altered by myokines such as irisin (Pedersen and Hoffman-Goetz, 2000;Pedersen, 2011;Myint et al, 2021), depending on the intensity and duration of activity (Lee, 2006). The realization that muscle used for movement also acts as a large endocrine organ that affects other systems is still new, and comparative studies that incorporate myokines into a life-history framework are needed.…”