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

Article Article scientifique Article Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin eng 2026-02-17 2026-03-20 author Jiang Xuewei University of Geneva, Department of Pathology and Immunology, 1211 Geneva, Switzerland. 400847 author Sellami-Dieudonné Sihem University of Geneva, Department of Pathology and Immunology, 1211 Geneva, Switzerland. 983899 Département de médecine (DEMED) Sihem Sellami-Dieudonne author Kessler Jérémy University of Geneva, Department of Cell Physiology and Metabolism, 1211 Geneva, Switzerland. 961781 Département de physiologie cellulaire et métabolisme (PHYME) author Bachmann Michaël University of Geneva, Department of Cell Physiology and Metabolism, 1211 Geneva, Switzerland.,Lib4RI - Library for the Research Institutes within the ETH Domain: Eawag, Empa, PSI & WSL, 8600 Dübendorf, Switzerland. 910175 author Noulet Fanny University of Geneva, Department of Pathology and Immunology, 1211 Geneva, Switzerland. 938959 author Russo Barbara University Hospitals of Geneva, Division of Dermatology and Venereology, 1205 Geneva, Switzerland. 864592 author Brembilla Nicolo University Hospitals of Geneva, Division of Dermatology and Venereology, 1205 Geneva, Switzerland. 703016 Département de médecine (DEMED) author Kaya Guerkan University Hospitals of Geneva, Division of Dermatology and Venereology, 1205 Geneva, Switzerland.,University Hospitals of Geneva, Division of Clinical Pathology, 1205 Geneva, Switzerland. 26603 Département de médecine (DEMED) author Ivanov Andrei I Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. author Shutova Maria University of Geneva, Department of Pathology and Immunology, 1211 Geneva, Switzerland.,University Hospitals of Geneva, Division of Dermatology and Venereology, 1205 Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 918718 author Wehrle-Haller Bernhard 0000-0002-1159-1147 University of Geneva, Department of Cell Physiology and Metabolism, 1211 Geneva, Switzerland. 116298 Département de physiologie cellulaire et métabolisme (PHYME) author Boehncke Wolf-Henning University of Geneva, Department of Pathology and Immunology, 1211 Geneva, Switzerland.,University Hospitals of Geneva, Division of Dermatology and Venereology, 1205 Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 779122 Département de médecine (DEMED) 115052 10.1016/j.isci.2026.115052 41847617 2589-0042 PMC12989852 https://www.sciencedirect.com/science/article/pii/S258900422600427X Transforming growth factor β (TGFβ) is a critical regulator of skin homeostasis and inflammation, including psoriasis. Multiple mechanisms can regulate TGFβ signaling, such as the activation of latent TGFβ1 through integrin-dependent pathways. We investigated the molecular mechanisms of TGFβ1 activation during cutaneous inflammation using reconstructed human epidermis treated with inflammatory cytokine cocktail. We 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 signaling in keratinocytes. Further, we 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, we reveal a mechanism of inflammation-driven TGFβ1 signaling regulation in human epidermis, linking cell mechanobiology to immunological outcomes, suggesting new therapeutic avenues. Cell biology Immunology Mechanobiology Dewey 612 Dewey 616.07 Dewey 616 Swiss National Science Foundation Regulation of integrin-dependent adhesion-signaling by growth factors and metabolic intermediates 185261 CH 137 Département de pathologie et immunologie 21F 134 Département de physiologie cellulaire et métabolisme 21C 56 Département de médecine 221 false 379 Migration cellulaire 645 576 Inflammation cutanée 919 478 Vieillissement cutané 809 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298207 iScience 29 3 6c335d80-fc4c-40dd-90bc-7d0b0e42857a Article (Published version) Public Article_scientifique_from_europePmc.pdf 21693811 application/pdf CC BY-4.0 48cf45d87a4730713175061f6c052128dd0678984efe96dd58cd08e6d0f52ab1 69c32845-81ff-48b5-a911-974f827c6b51 Appendix Public mmc1.pdf 576889 application/pdf 0d3af2282074c82cd866ca018d949e9b3db430d53862b1ce53bcb529ea4e0998 Vignette Public 1-s2.0-S258900422600427X-fx1_lrg.jpg 263250 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de médecine

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Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin	iScience	2026	33	14
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