Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin
Transforming growth factor β (TGFβ) is a critical regulator of skin homeostasis and inflammation, including psoriasis. Multiple mechanisms can regulate TGFβ signalling, such as the activation of latent TGFβ1 through integrin-dependent pathways. The authors of this article investigated the molecular mechanisms of TGFβ1 activation during cutaneous inflammation using reconstructed human epidermis treated with inflammatory cytokine cocktail. They report αvβ6 integrin upregulation and enhanced binding of TGFβ1 latency-associated peptide (LAP), which, however, did not result in active TGFβ1 release, restricting the TGFβ1 activation to paracrine signalling in keratinocytes. Further, they identify a mechanosensitive positive feedback loop, that occurs downstream of inflammatory stimuli and involves TGFβ-mediated activation of mechanotransduction, further promoting mechanodependent, αvβ6-mediated TGFβ1 activation in keratinocytes. Thus, they reveal a mechanism of inflammation-driven TGFβ1 signalling regulation in human epidermis, linking cell mechanobiology to immunological outcomes, suggesting new therapeutic avenues.
Full article: https://doi.org/10.1016/j.isci.2026.115052
Graphical Abstract. ©Boehncke WH UNIGE
Citation:
Jiang X, Sellami S, Kessler J, Bachmann M, Noulet F, Russo B, Brembilla NC, Kaya G, Ivanov AI, Shutova MS, Wehrle-Haller B, Boehncke WH. Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin. iScience. 2026 Feb 17;29(3):115052. doi: 10.1016/j.isci.2026.115052. Epub 2026 Mar 20. PMID: 41847617; PMCID: PMC12989852.
WHY IS IT IMPORTANT?
Psoriasis is a common inflammatory skin disease where skin cells grow and behave abnormally. This study uncovers how inflammation activates TGFβ1, a key molecule involved in regulating immune responses and skin cell behaviour.
The researchers show that inflammation increases the expression of a receptor called αvβ6 integrin, which activates TGFβ1 through mechanical forces generated inside skin cells. This creates a self-amplifying loop that sustains inflammation.
This is important because it reveals a new way that inflammation is maintained in the skin, not just through immune cells, but also through physical forces within cells. Understanding this could lead to new treatments that target these mechanisms more precisely, especially for patients who do not respond well to current therapies.