| First Author | Poirier A | Year | 2023 |
| Journal | Immun Ageing | Volume | 20 |
| Issue | 1 | Pages | 31 |
| PubMed ID | 37400834 | Mgi Jnum | J:337863 |
| Mgi Id | MGI:7506697 | Doi | 10.1186/s12979-023-00350-y |
| Citation | Poirier A, et al. (2023) TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFalpha. Immun Ageing 20(1):31 |
| abstractText | BACKGROUND: Human aging is characterized by a state of chronic inflammation, termed inflammaging, for which the causes are incompletely understood. It is known, however, that macrophages play a driving role in establishing inflammaging by promoting pro-inflammatory rather than anti-inflammatory responses. Numerous genetic and environmental risk factors have been implicated with inflammaging, most of which are directly linked to pro-inflammatory mediators IL-6, IL1Ra, and TNFalpha. Genes involved in the signaling and production of those molecules have also been highlighted as essential contributors. TAOK3 is a serine/threonine kinase of the STE-20 kinase family that has been associated with an increased risk of developing auto-immune conditions in several genome-wide association studies (GWAS). Yet, the functional role of TAOK3 in inflammation has remained unexplored. RESULTS: We found that mice deficient in the serine/Threonine kinase Taok3 developed severe inflammatory disorders with age, which was more pronounced in female animals. Further analyses revealed a drastic shift from lymphoid to myeloid cells in the spleens of those aged mice. This shift was accompanied by hematopoietic progenitor cells skewing in Taok3(-/-) mice that favored myeloid lineage commitment. Finally, we identified that the kinase activity of the enzyme plays a vital role in limiting the establishment of proinflammatory responses in macrophages. CONCLUSIONS: Essentially, Taok3 deficiency promotes the accumulation of monocytes in the periphery and their adoption of a pro-inflammatory phenotype. These findings illustrate the role of Taok3 in age-related inflammation and highlight the importance of genetic risk factors in this condition. |
