| First Author | Kang Y | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 13 | Pages | 3493-3506 |
| PubMed ID | 29590618 | Mgi Jnum | J:271204 |
| Mgi Id | MGI:6278461 | Doi | 10.1016/j.celrep.2018.02.071 |
| Citation | Kang Y, et al. (2018) Telomere Dysfunction Disturbs Macrophage Mitochondrial Metabolism and the NLRP3 Inflammasome through the PGC-1alpha/TNFAIP3 Axis. Cell Rep 22(13):3493-3506 |
| abstractText | Immune and inflammation dysregulation have been associated with the aging process and contribute to age-related disorders, but the underlying mechanism remains elusive. Here, we employed late-generation Terc knockout (Terc(-/-)) mice to investigate the impact of telomere dysfunction on the host defense and function of innate immune cells. Terc(-/-) mice displayed exaggerated lung inflammation and increased mortality upon respiratory staphylococcal infection, although their pathogen-clearing capacity was uncompromised. Mechanistically, we found that telomere dysfunction caused macrophage mitochondrial abnormality, oxidative stress, and hyperactivation of the NLRP3 inflammasome. The ubiquitin-editing enzyme TNFAIP3, together with PGC-1alpha, was critically involved in the regulation of mitochondrial and inflammatory gene expression and essential for the homeostatic role of telomeres. Together, the study reveals a regulatory paradigm that connects telomeres to mitochondrial metabolism, innate immunity, and inflammation, shedding light on age-related pathologies. |
