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

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dc.contributor.authorHoste, Esther
dc.contributor.authorMaueröder, Christian
dc.contributor.authorHove, Lisette van
dc.contributor.authorCatrysse, Leen
dc.contributor.authorVikkula, Hanna-Kaiza
dc.contributor.authorSze, Mozes
dc.contributor.authorMaes, Bastiaan
dc.contributor.authorKarjosukarso, Dyah
dc.contributor.authorMartens, Liesbet
dc.contributor.authorGoncalves, Amanda
dc.contributor.authorParthoens, Eef
dc.contributor.authorRoelandt, Ria
dc.contributor.authorDeclercq, Wim
dc.contributor.authorFuentes, Ignacia
dc.contributor.authorPalisson, Francis
dc.contributor.authorGonzalez, Sergio
dc.contributor.authorSalas-Alanis, Julio C.
dc.contributor.authorBoon, Louis
dc.contributor.authorHuebener, Peter
dc.contributor.authorMulder, Klaas Willem
dc.contributor.authorRavichandran, Kodi
dc.contributor.authorSaeys, Yvan
dc.contributor.authorSchwabe, Robert Felix
dc.contributor.authorLoo, Geert van
dc.date.accessioned2020-04-02T18:24:52Z
dc.date.available2020-04-02T18:24:52Z
dc.date.issued2019
dc.description.abstractRegenerative 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.extent18 p.
dc.identifier.citationCell Reports. 2019 Nov 26;29(9):2689-2701
dc.identifier.urihttp://hdl.handle.net/11447/3205
dc.identifier.urihttps://doi.org/10.1016/j.celrep.2019.10.104
dc.language.isoen
dc.subjectHMGB1
dc.subjectTNF
dc.subjectDiabetes
dc.subjectEpidermolysis bullosa
dc.subjectInnate immunity
dc.subjectNeutrophil extracellular traps
dc.subjectSkin inflammation
dc.subjectTumor microenvironment
dc.subjectWound healing
dc.titleEpithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation
dc.typeArticle

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