Article | Published:

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

Nature Immunology volume 17, pages 13731380 (2016) | Download Citation

  • A Corrigendum to this article was published on 16 November 2016

This article has been updated

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.

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Change history

  • 10 October 2016

    In the version of this article initially published online, the immunoblots in Figures 1a, 5a, 5b, 5c, 5d, 5f, 6a, 6b, 7a, 7b, 8a and 8b were in color. These have been replaced with black and white immunoblots. The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank the Wellcome Trust Sanger Institute Mouse Genetics Project (Sanger MGP) and its funders for the mutant mouse line Trim29, and the European Mouse Mutant Archive (http://www.emmanet.org) partner from which the mouse line was received. Funding and associated primary phenotypic information is provided at the Sanger website (http://www.sanger.ac.uk/mouseportal). We also thank L. Minze for operational support. Supported by the US National Institutes of Health (R01AI080779 to X.C.L.).

Author information

Author notes

    • Yong-Jun Liu

    Present address: Sanofi, Cambridge, Massachusetts, USA.

Affiliations

  1. Immunobiology and Transplant Research Center, Houston Methodist Research Institute, Houston, Texas, USA.

    • Junji Xing
    • , Bin Yuan
    • , Zhuo Wang
    • , Li Jia
    • , Rui Jin
    • , Xian Chang Li
    •  & Zhiqiang Zhang
  2. Medimmune, Gaithersburg, Maryland, USA.

    • Leiyun Weng
    • , Hongbo Lu
    •  & Yong-Jun Liu
  3. Department of Surgery, Weill Cornell Medical College of Cornell University, New York, New York, USA.

    • Xian Chang Li
    •  & Zhiqiang Zhang
  4. Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.

    • Yong-Jun Liu

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Contributions

J.X. designed and performed most of the experiments; L.W., B.Y., Z.W., L.J., R.J. and H.L. helped with some of the experiments; X.C.L., Y.-J.L. and Z.Z. wrote the manuscript; and Z.Z. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Yong-Jun Liu or Zhiqiang Zhang.

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DOI

https://doi.org/10.1038/ni.3580

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