Identification of the E3 ligase TRIM29 as a critical checkpoint regulator of NK cell functions

Yaling Dou, Junji Xing, Gangcheng Kong, Guangchuan Wang, Xiaohua Lou, Xiang Xiao, Eric Vivier, Xian C Li, Zhiqiang Zhang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

NK cells play an important role in immune surveillance and protective immunity, mainly through rapid cytokine release and cytolytic activities. But how such responses are negatively regulated remains poorly defined. In this study, we demonstrated that the E3 ubiquitin ligase TRIM29 is a crucial regulator of NK cell functions. We found that TRIM29 was not expressed in resting NK cells, but was readily upregulated following activation, especially after IL-12 plus IL-18 stimulation. The levels of TRIM29 expression were inversely correlated with IFN-g production by NK cells, suggesting that TRIM29 inhibits NK cell functions. Indeed, deficiency of TRIM29, specifically in NK cells, resulted in an enhanced IFN-g production and consequently protected mice from murine CMV infection. Mechanistically, we showed that once induced in NK cells, TRIM29 ubiquitinates and degrades the TGF-b–activated kinase 1 binding protein 2 (TAB2), a key adaptor protein in IFN-g production by NK cells. These results identify TRIM29 as a negative regulator of NK cell functions and may have important clinical implications.

Original languageEnglish (US)
Pages (from-to)873-880
Number of pages8
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume203
Issue number4
Early online dateJul 3 2019
DOIs
StatePublished - Aug 15 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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