{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:14:16Z","timestamp":1788495256897,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":167,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFC1000805"],"award-info":[{"award-number":["2016YFC1000805"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Intestinal mucositis is the major side effect during abdominal or pelvic radiotherapy, but the underlying immunogen remains to be further characterised and few radioprotective agents are available. This study investigated the role of dsDNA\u2010triggered inflammasomes in intestinal mucositis during radiotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pro\u2010inflammatory cytokines were detected by ELISA. Radiation\u2010induced intestinal injury in mice was analyzed by means of survival curves, body weight, HE staining of intestines, and intestinal barrier integrity. Western blot, immunofluorescence staining, co\u2010immunoprecipitation assay and flow cytometry were used to investigate the regulatory role of dsDNA on inflammasomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we show that a high level of IL\u20101\u03b2 and IL\u201018 is associated with diarrhoea in colorectal cancer (CRC) patients during radiotherapy, which accounts for intestinal radiotoxicity. Subsequently, we found that the dose\u2010dependently released dsDNA from the intestinal epithelial cells (IECs) serves as the potential immunogenic molecule for radiation\u2010induced intestinal mucositis. Our results further indicate that the released dsDNA transfers into the macrophages in an HMGB1\/RAGE\u2010dependent manner and then triggers absent in melanoma 2 (AIM2) inflammasome activation and the IL\u20101\u03b2 and IL\u201018 secretion. Finally, we show that the FDA\u2010approved disulfiram (DSF), a newly identified inflammasome inhibitor, could mitigate intestinal radiotoxicity by controlling inflammasome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicate that the extracellular self\u2010dsDNA released from the irradiated IECs is a potential immunogen to stimulate immune cells and trigger the subsequent intestinal mucositis, while blunting the dsDNA\u2010triggered inflammasome in macrophages may represent an exciting therapeutic strategy for side effects control during abdominal radiotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1452","type":"journal-article","created":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T12:52:51Z","timestamp":1687006371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Released dsDNA\u2010triggered inflammasomes serve as intestinal radioprotective targets"],"prefix":"10.1002","volume":"12","author":[{"given":"Long","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"},{"name":"Shigatse Branch, Xinqiao Hospital, Army 953 Hospital Army Medical University Shigatse China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Geriatric Cardiovascular Disease Research and Treatment Center, 252 Hospital of PLA Baoding China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Yao","sequence":"additional","affiliation":[{"name":"Integrative Cancer Center &amp; Cancer Clinical Research Center, Sichuan Cancer Center, School of Medicine, Sichuan Cancer Hospital &amp; Institute University of Electronic Science and Technology of China Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oncology Western Theater General Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongdan","family":"Chen","sequence":"additional","affiliation":[{"name":"Breast and Thyroid Surgical Department, Chongqing General Hospital University of Chinese Academy of Sciences Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyong","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-738X","authenticated-orcid":false,"given":"Chunmeng","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21565"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0064-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.46"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15149"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviscsurg.2018.09.002"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060191"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166202"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR15486.1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf7532"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-313789"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2000.02013.x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.07.1736"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i22.3043"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534735418794885"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06085-5"},{"key":"e_1_2_11_18_1","first-page":"3508","article-title":"The protective role of short\u2010chain fatty acids acting as signal molecules in chemotherapy\u2010 or radiation\u2010induced intestinal inflammation","volume":"10","author":"Tian T","year":"2020","journal-title":"Am J Cancer Res"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75675-5"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121886"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00425-z"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/jrr\/rraa062"},{"key":"e_1_2_11_23_1","article-title":"Protective effects of crocetin against radiation\u2010induced injury in intestinal\u00a0epithelial cells","volume":"2020","author":"Zhang C","year":"2020","journal-title":"Biomed Res Int"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/8653783","article-title":"Glycyrrhizin ameliorates radiation enteritis in mice accompanied by the regulation of the HMGB1\/TLR4 pathway","volume":"2020","author":"Zhang XM","year":"2020","journal-title":"Evid Based Complement Alternat Med"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0311-9"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0054-1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.54"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2195-8"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109597"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.02.010"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.039"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2174-3"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.01.023"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017080863"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24655"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0960"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314279"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-020-00845-6"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201901048"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70504-7"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107830"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72340"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2669"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106761"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07725"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8827"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.040"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0372-z"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.009"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0278-6"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2630"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0669-6"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9818"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25016"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14338-5"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202000542"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou305"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12584"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322691111"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-754994"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.03.012"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay9097"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.136"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.06.001"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.06.074"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2015.12.004"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0123-y"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.003"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1551-2"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-311909"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7114"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13130"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1078958"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T13:45:42Z","timestamp":1729604742000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":72,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/cti2.1452"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1452","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"2022-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1452"}}