{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Baatarjav C"],"funding":["MEXT | Japan Society for the Promotion of Science","JMU Graduate Student Start-up Award and Student Research Award","Jichi Medical University"],"pagination":["2487-2502"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9750976"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(12)"],"pubmed_abstract":["Rhabdomyolysis is a severe condition that commonly leads to acute kidney injury (AKI). While double-stranded DNA (dsDNA) released from injured muscle can be involved in its pathogenesis, the exact mechanism of how dsDNA contributes to rhabdomyolysis-induced AKI (RIAKI) remains obscure. A dsDNA sensor, absent in melanoma 2 (AIM2), forms an inflammasome and induces gasdermin D (GSDMD) cleavage resulting in inflammatory cell death known as pyroptosis. In this study using a mouse model of RIAKI, we found that Aim2-deficiency led to massive macrophage accumulation resulting in delayed functional recovery and perpetuating fibrosis in the kidney. While Aim2-deficiency compromised RIAKI-induced kidney macrophage pyroptosis, it unexpectedly accelerated aberrant inflammation as demonstrated by CXCR3<sup>+</sup>CD206<sup>+</sup> macrophage accumulation and activation of TBK1-IRF3/NF-κB. Kidney macrophages with intact AIM2 underwent swift pyroptosis without IL-1β release in response to dsDNA. On the other hand, dsDNA-induced Aim2-deficient macrophages escaped from swift pyroptotic elimination and instead engaged STING-TBK1-IRF3/NF-κB signalling, leading to aggravated inflammatory phenotypes. Collectively, these findings shed light on a hitherto unknown immunoregulatory function of macrophage pyroptosis. dsDNA-induced rapid macrophage cell death potentially serves as an anti-inflammatory program and determines the healing process of RIAKI."],"journal":["Cell death and differentiation"],"pubmed_title":["dsDNA-induced AIM2 pyroptosis halts aberrant inflammation during rhabdomyolysis-induced acute kidney injury."],"pmcid":["PMC9750976"],"funding_grant_id":["21K06875","19K21319","21K08114","20K17290"],"pubmed_authors":["Karasawa T","Baatarjav C","Komada T","Matsumura T","Takahashi M","Yamada N","Sampilvanjil A"],"additional_accession":[]},"is_claimable":false,"name":"dsDNA-induced AIM2 pyroptosis halts aberrant inflammation during rhabdomyolysis-induced acute kidney injury.","description":"Rhabdomyolysis is a severe condition that commonly leads to acute kidney injury (AKI). While double-stranded DNA (dsDNA) released from injured muscle can be involved in its pathogenesis, the exact mechanism of how dsDNA contributes to rhabdomyolysis-induced AKI (RIAKI) remains obscure. A dsDNA sensor, absent in melanoma 2 (AIM2), forms an inflammasome and induces gasdermin D (GSDMD) cleavage resulting in inflammatory cell death known as pyroptosis. In this study using a mouse model of RIAKI, we found that Aim2-deficiency led to massive macrophage accumulation resulting in delayed functional recovery and perpetuating fibrosis in the kidney. While Aim2-deficiency compromised RIAKI-induced kidney macrophage pyroptosis, it unexpectedly accelerated aberrant inflammation as demonstrated by CXCR3<sup>+</sup>CD206<sup>+</sup> macrophage accumulation and activation of TBK1-IRF3/NF-κB. Kidney macrophages with intact AIM2 underwent swift pyroptosis without IL-1β release in response to dsDNA. On the other hand, dsDNA-induced Aim2-deficient macrophages escaped from swift pyroptotic elimination and instead engaged STING-TBK1-IRF3/NF-κB signalling, leading to aggravated inflammatory phenotypes. Collectively, these findings shed light on a hitherto unknown immunoregulatory function of macrophage pyroptosis. dsDNA-induced rapid macrophage cell death potentially serves as an anti-inflammatory program and determines the healing process of RIAKI.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-21T23:11:48.469Z","creation":"2025-04-05T19:02:18.11Z"},"accession":"S-EPMC9750976","cross_references":{"pubmed":["35739254"],"doi":["10.1038/s41418-022-01033-9"]}}