Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin

Based on this study's findings, inflammatory stimuli upregulate αvβ6 integrin, which binds the Latency-Associated Peptide (LAP). This interaction triggers a mechanosensitive feedback loop where TGFβ-mediated mechanotransduction further promotes the activation of Transforming Growth Factor β1 (TGFβ1) within the keratinocyte microenvironment.

The researchers found that although αvβ6 integrin expression increased and enhanced binding of the Latency-Associated Peptide (LAP) occurred, active Transforming Growth Factor β1 (TGFβ1) was not released. Instead, the activation was restricted to paracrine signaling among keratinocytes in the reconstructed human epidermis.

The researchers utilized reconstructed human epidermis (RHE) because it replicates the three-dimensional architecture of human skin. This model allowed the team to observe how an inflammatory cytokine cocktail induces receptor upregulation and mechanical feedback loops that are not easily captured in simpler cell cultures.

The study's findings are confined to paracrine signaling within the epidermal layer. The authors observed that the αvβ6-mediated activation of Transforming Growth Factor β1 (TGFβ1) did not result in the release of the active protein into the surrounding medium, limiting its effects to local keratinocyte interactions.

The study's authors propose that targeting the mechanosensitive positive feedback loop involving αvβ6 integrin could offer new therapeutic avenues. They suggest that disrupting this link between cell mechanobiology and immunological outcomes may help manage chronic inflammatory conditions like psoriasis in human skin.