| First Author | Du H | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 7 | Pages | 107090 |
| PubMed ID | 37416470 | Mgi Jnum | J:354254 |
| Mgi Id | MGI:7508799 | Doi | 10.1016/j.isci.2023.107090 |
| Citation | Du H, et al. (2023) Suppression of TREX1 deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response. iScience 26(7):107090 |
| abstractText | TREX1 encodes a major DNA exonuclease and mutations of this gene are associated with type I interferonopathies in human. Mice with Trex1 deletion or mutation have shortened life spans accompanied by a senescence-associated secretory phenotype. However, the contribution of cellular senescence in TREX1 deficiency-induced type I interferonopathies remains unknown. We found that features of cellular senescence present in Trex1(-/-) mice are induced by multiple factors, particularly DNA damage. The cGAS-STING and DNA damage response pathways are required for maintaining TREX1 deletion-induced cellular senescence. Inhibition of the DNA damage response, such as with Checkpoint kinase 2 (CHK2) inhibitor, partially alleviated progression of type I interferonopathies and lupus-like features in the mice. These data provide insights into the initiation and development of type I interferonopathies and lupus-like diseases, and may help inform the development of targeted therapeutics. |
