Integrin alpha-V beta-6 (αVβ6) and Integrin alpha-V beta-8 (αVβ8) (αVβ6 and αVβ8)

Integrin alpha-V beta-6 (αVβ6) and alpha-V beta-8 (αVβ8) are heterodimeric cell surface receptors that serve as key activators of Transforming Growth Factor-beta (TGF-β) (1). While αVβ6 is primarily expressed on epithelial cells during injury, inflammation, and malignancy, αVβ8 is found on both epithelial cells and immune cells, most notably dendritic cells and regulatory T-lymphocytes (Tregs) (2, 3). These integrins recognize the RGD tripeptide motif in the Latency Associated Peptide (LAP) of TGF-β, facilitating its release into an active form through mechanical tension or proteolytic cleavage (4). In the immune system, αVβ8-mediated TGF-β activation on lymphocytes and dendritic cells is essential for maintaining immune tolerance and suppressing anti-tumor immunity (5). Consequently, dual inhibition of αVβ6 and αVβ8 is a therapeutic strategy aimed at treating fibrotic diseases like idiopathic pulmonary fibrosis and enhancing the efficacy of cancer immunotherapies by reducing TGF-β-mediated immunosuppression (6). It should be noted that the inclusion of αVβ6 as a lymphocyte-expressed integrin is biologically inaccurate, as its expression is largely restricted to the epithelium (7).

Other names

ITGAV-ITGB6ITGAV-ITGB8Alpha-V beta-6Alpha-V beta-8CD51/ITGB6CD51/ITGB8

Inhibition of the RGD-mediated binding of alpha-V integrins to the Latency Associated Peptide (LAP), preventing the mechanical or proteolytic activation of latent TGF-beta1 and TGF-beta3.