Myint Phyoe Kyawe, Ito Atsushi, Appiah Michael G, Obeng Gideon, Darkwah Samuel, Kawamoto Eiji, Gaowa Arong, Park Eun Jeong, Shimaoka Motomu
Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Japan.
Department of Cardiothoracic and Vascular Surgery, Mie University Graduate School of Medicine, Japan.
Biochem Biophys Rep. 2021 Mar 8;26:100977. doi: 10.1016/j.bbrep.2021.100977. eCollection 2021 Jul.
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.
鸢尾素是一种从骨骼肌释放的肌动蛋白，最近被发现可作为间充质细胞上表达的整合素αVβ5、αVβ1和α5β1的配体，从而在骨骼、骨骼肌和脂肪组织的代谢重塑中发挥重要作用。尽管鸢尾素在慢性炎症中的免疫调节作用已有文献记载，但其与淋巴细胞整合素的相互作用尚待阐明。在此，我们表明鸢尾素可支持人和小鼠淋巴细胞的细胞黏附。使用一组整合素抑制抗体进行的细胞黏附试验表明，鸢尾素介导的淋巴细胞黏附涉及多种整合素，不仅包括α4β1和α5β1，还包括白细胞特异性αLβ2和α4β7。重要的是，缺乏β1整合素表达的小鼠淋巴细胞TK-1细胞表现出αLβ2和α4β7介导的对鸢尾素的细胞黏附。鸢尾素也已被证明可与纯化的重组整合素αLβ2和α4β7蛋白结合。因此，鸢尾素是整合素αLβ2和α4β7的一种新型配体，能够独立于β1整合素支持淋巴细胞的细胞黏附。这些结果表明，鸢尾素可能在调节炎症血管中淋巴细胞的黏附和迁移方面发挥重要作用。
