| First Author | Xing J | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 12 | Pages | 1373-1380 |
| PubMed ID | 27695001 | Mgi Jnum | J:277470 |
| Mgi Id | MGI:6330983 | Doi | 10.1038/ni.3580 |
| Citation | Xing J, et al. (2016) Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract. Nat Immunol 17(12):1373-1380 |
| abstractText | The respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. Here we found that the E3 ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar macrophages, the expression of type I interferons and the production of proinflammatory cytokines in the lungs. We found that deletion of TRIM29 enhanced macrophage production of type I interferons and protected mice from infection with influenza virus, while challenge of Trim29(-/-) mice with Haemophilus influenzae resulted in lethal lung inflammation due to massive production of proinflammatory cytokines by macrophages. Mechanistically, we demonstrated that TRIM29 inhibited interferon-regulatory factors and signaling via the transcription factor NF-kappaB by degrading the adaptor NEMO and that TRIM29 directly bound NEMO and subsequently induced its ubiquitination and proteolytic degradation. These data identify TRIM29 as a key negative regulator of alveolar macrophages and might have important clinical implications for local immunity and immunopathology. |
