2. Academic Validation
  3. Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract

  • Nat Immunol. 2016 Dec;17(12):1373-1380. doi: 10.1038/ni.3580.
Junji Xing 1,  Leiyun Weng 2,  Bin Yuan 1,  Zhuo Wang 1,  Li Jia 1,  Rui Jin 1,  Hongbo Lu 2,  Xian Chang Li 1 3,  Yong-Jun Liu 2 4,  Zhiqiang Zhang 1 3
Affiliations

Affiliations

  • 1 Immunobiology and Transplant Research Center, Houston Methodist Research Institute, Houston, Texas, USA.
  • 2 Medimmune, Gaithersburg, Maryland, USA.
  • 3 Department of Surgery, Weill Cornell Medical College of Cornell University, New York, New York, USA.
  • 4 Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
PMID: 27695001 DOI: 10.1038/ni.3580
Abstract

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-κB 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.

Figures