Molecular requirements for TGF-β1 activation mediated by integrin αVβ8 or monoclonal antibodies
(2026)
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- (en) Activity of the immunosuppressive TGF-β1 cytokine is tightly regulated at a post-translational level, through cell-type specific processes collectively called “latent TGF-β1 activation”. On the surface of regulatory T lymphocytes (Tregs), latent TGF-β1 is presented by transmembrane protein GARP to integrin αVβ8, leading to activation of the cytokine through mechanisms that are still not completely understood. Whether αVβ8-mediated activation requires cytoskeleton-driven forces, and whether it can lead to TGF-β1 activity in neighboring cells (i.e. paracrine activity) has long been debated. In this work, we used cDNA screening and cell-based assays to better characterize TGF-β1 activation by Tregs. Based on our results, we propose a model in which integrin αVβ8 passively activates TGF-β1 by transmitting cell-generated tensile forces without direct interaction with the cytoskeleton, allowing paracrine TGF-β1 activity. Our work unambiguously establishes that TGF-β1 produced by Tregs can suppress neighboring immune cells.
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Jamez, M. (2026). Molecular requirements for TGF-β1 activation mediated by integrin αVβ8 or monoclonal antibodies. https://hdl.handle.net/2078.5/276961