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Here we report a novel concept that cells can signal chromatin damage from the nucleus back to the surrounding tissue through the cytokine interleukin-1alpha (IL-1\u03b1). Thus, in addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, IL-1\u03b1 could directly sense DNA damage and act as signal for genotoxic stress without loss of cell integrity. Here we demonstrate localization of the cytokine to DNA-damage sites and its subsequent secretion. Interestingly, its nucleo-cytosolic shuttling after DNA damage sensing is regulated by histone deacetylases (HDAC) and IL-1\u03b1 acetylation. To demonstrate the physiological significance of this newly discovered mechanism, we used IL-1\u03b1 knockout mice and show that IL-1\u03b1 signaling after UV skin irradiation and DNA damage is important for triggering a sterile inflammatory cascade <jats:italic>in vivo<\/jats:italic> that contributes to efficient tissue repair and wound healing.<\/jats:p>","DOI":"10.1038\/srep14756","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T08:58:33Z","timestamp":1444121913000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["IL-1\u03b1 is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity"],"prefix":"10.1038","volume":"5","author":[{"given":"Idan","family":"Cohen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peleg","family":"Rider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vornov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Tomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cicerone","family":"Tudor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Wegner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Brondani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Freudenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Mittler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Ferrando-May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Dinarello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron N.","family":"Apte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,6]]},"reference":[{"key":"BFsrep14756_CR1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","volume":"27","author":"CA Dinarello","year":"2009","unstructured":"Dinarello, C. 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