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Previous studies found that TLR9\u2010related signalling pathways are associated with the inflammatory response of cardiac myocytes, mitochondrial dysfunction and cardiomyocyte death, but it remains unclear whether TLR9 could influence DOX\u2010induced heart injury. Our current data imply that DOX\u2010induced cardiotoxicity is ameliorated by TLR9 deficiency both in vivo and in vitro, manifested as improved cardiac function and reduced cardiomyocyte apoptosis and oxidative stress. Furthermore, the deletion of TLR9 rescued DOX\u2010induced abnormal autophagy flux in vivo and in vitro. However, the inhibition of autophagy by 3\u2010MA abolished the protective effects of TLR9 deletion on DOX\u2010induced cardiotoxicity. Moreover, TLR9 ablation suppressed the activation of p38 MAPK during DOX administration and may promote autophagy via the TLR9\u2010p38 MAPK signalling pathway. Our study suggests that the deletion of TLR9 exhibits a protective effect on doxorubicin\u2010induced cardiotoxicity by enhancing p38\u2010dependent autophagy. This finding could be used as a basis for the development of a prospective therapy against DOX\u2010induced cardiotoxicity.<\/jats:p>","DOI":"10.1111\/jcmm.15719","type":"journal-article","created":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T11:18:56Z","timestamp":1596971936000},"page":"10913-10923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["TLR9 deficiency alleviates doxorubicin\u2010induced cardiotoxicity via the regulation of autophagy"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-176X","authenticated-orcid":false,"given":"Zhen","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan China"},{"name":"Cardiovascular Research Institute of Wuhan University Wuhan 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