αvβ8

Integrin αvβ8 functions primarily as an activator of latent transforming growth factor β (TGF-β), regulating immune tolerance and inflammatory responses^[1][2]. Mechanistically, αvβ8 expressed on regulatory T cells (Tregs) enables the activation of TGF-β, which suppresses effector T-cell-mediated inflammation in ongoing immune responses^[1]. Compared with other αv integrins, αvβ8 exhibits distinct cell-type expression and preferentially mediates TGF-β activation in dendritic cells, Tregs, and tumor-associated immune cells^[1][3][2]. In tumor biology, αvβ8 supports immune evasion by inhibiting cytotoxic CD8+ T-cell activity and can enhance tumor progression in colon cancer and glioblastoma models^[3][4][5]. αvβ8 also contributes to pathological angiogenesis in astrocytoma by modulating latent TGF-β availability and endothelial cell signaling^[6]. Experimental models using αvβ8-blocking antibodies or genetic knockouts have demonstrated that selective inhibition restores immune function, reduces tumor growth, and ameliorates fibrosis, indicating its therapeutic potential^[7][3][4][2]. Unlike related integrins such as αvβ6, αvβ8 maintains a constitutively extended-closed conformation, allowing highly selective targeting with designed miniprotein inhibitors^[8]. Agonist or inhibitor studies in immune thrombocytopenia, fibrosis, and cancer models show that modulating αvβ8 activity can precisely influence TGF-β signaling, cell migration, and immunoregulation^[7][2][8]. Collectively, αvβ8 represents a critical node for TGF-β-dependent cellular processes and a distinct pharmacological target among αv integrin isoforms^[1][8][5].

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