2. Academic Validation
  3. TRIM10 binds to IFN-α/β receptor 1 to negatively regulate type I IFN signal transduction

TRIM10 binds to IFN-α/β receptor 1 to negatively regulate type I IFN signal transduction

  • Eur J Immunol. 2021 Jul;51(7):1762-1773. doi: 10.1002/eji.202049073.
Mengmeng Guo 1,  Wenyan Cao 1,  Shengwen Chen 1,  Renyun Tian 1,  Luoling Wang 1,  Qian Liu 1,  Lini Zhang 1,  Zhenghao Wang 1,  Ming Zhao 2,  Qianjin Lu 2,  Haizhen Zhu 1 3
Affiliations

Affiliations

  • 1 Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, China.
  • 2 Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China.
  • 3 Research Center of Cancer Prevention and Treatment, Translational Medicine Research Center of Liver Cancer, Hunan Provincial Tumor Hospital, Changsha, China.
PMID: 33811647 DOI: 10.1002/eji.202049073
Abstract

The type I interferon (IFN-I) system is important for Antiviral and Anticancer immunity. Prolonged activation of IFN/JAK/STAT signaling is closely associated with autoimmune diseases. TRIM10 dysfunction may be associated closely with certain autoimmune disorders. Here, we observed that the serum TRIM10 protein level is lower in patients with systemic lupus erythematosus than in healthy control subjects. We speculated the possible involvement of TRIM10-induced modulation of the IFN/JAK/STAT signaling pathway in systemic lupus erythematosus. In line with our hypothesis, TRIM10 inhibited the activation of JAK/STAT signaling pathway triggered by various stimuli. TRIM10 restricted the IFN-I/JAK/STAT signaling pathway, which was independent of its E3 Ligase activity. Mechanistically, TRIM10 interacted with the intracellular domain of IFNAR1 and blocked the association of IFNAR1 with Tyk2. These data suggest the possible TRIM10 suppresses IFN/JAK/STAT signaling pathway through blocking the interaction between IFNAR1 and Tyk2. Targeting TRIM10 is a potential strategy for treating autoimmune diseases.

Keywords

IFNAR1; SLE; TRIM10; innate immunity; type I interferon.

Figures