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Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation

Show simple item record Hoste, Esther Maueröder, Christian Hove, Lisette van Catrysse, Leen Vikkula, Hanna-Kaiza Sze, Mozes Maes, Bastiaan Karjosukarso, Dyah Martens, Liesbet Goncalves, Amanda Parthoens, Eef Roelandt, Ria Declercq, Wim Fuentes, Ignacia Palisson, Francis Gonzalez, Sergio Salas-Alanis, Julio C. Boon, Louis Huebener, Peter Mulder, Klaas Willem Ravichandran, Kodi Saeys, Yvan Schwabe, Robert Felix Loo, Geert van 2020-04-02T18:24:52Z 2020-04-02T18:24:52Z 2019
dc.identifier.citation Cell Rep. 2019 Nov 26;29(9):2689-2701
dc.description.abstract Regenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a dangerassociated molecular pattern contributing to inflammatory pathologies. We show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives tumor formation. In wounds of mice lacking HMGB1 selectively in keratinocytes, a marked reduction in neutrophil extracellular trap (NET) formation is observed. Pharmacological targeting of HMGB1 or NETs prevents skin tumorigenesis and accelerates wound regeneration. HMGB1-dependent NET formation and skin tumorigenesis is orchestrated by tumor necrosis factor (TNF) and requires RIPK1 kinase activity. NETs are present in the microenvironment of keratinocyte-derived tumors in mice and lesional and tumor skin of patients suffering from recessive dystrophic epidermolysis bullosa, a disease in which skin blistering predisposes to tumorigenesis. We conclude that tumorigenicity of the wound microenvironment depends on epithelial-derived HMGB1 regulating NET formation, thereby establishing a mechanism linking reparative inflammation to tumor initiation.
dc.format.extent 18 p.
dc.language.iso en
dc.subject HMGB1
dc.subject TNF
dc.subject Diabetes
dc.subject Epidermolysis bullosa
dc.subject Innate immunity
dc.subject Neutrophil extracellular traps
dc.subject Skin inflammation
dc.subject Tumor microenvironment
dc.subject Wound healing
dc.title Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation
dc.type Article

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