TRNA derived fragment (tRF)-3009 participates in modulation of IFN-α-induced CD4⁺ T cell oxidative phosphorylation in lupus patients.

ABSTRACT:

Background

Accumulating evidence suggests tRNA-derived fragments (tRFs) play important roles in cellular homeostasis. Here we aimed to explore aberrant expression of tRFs in CD4⁺ T cells from patients with systemic lupus erythematosus (SLE) and their potential function in the SLE pathogenesis.

Methods

First, small RNA sequencing was performed on CD4⁺ T cells from four SLE patients and three healthy controls (HCs). Candidate tRFs were then validated in CD4⁺ T cells from 97 SLE patients and their relevant disease controls using qRT-PCR. Then sequencing was used to investigate the profiles of HC-derived CD4⁺ T cells transfected with tRF-3009. Lastly, tRF-3009 siRNA or tRF-3009 mimics were transfected into CD4⁺ T cells with/without IFN-α. Changes in oxygen consumption rate (OCR), ATP, and ROS production were analyzed.

Results

We identified 482 differentially expressed tRFs from SLE CD4⁺ T cells and chose tRF-3009 for further analysis due to its upregulation and the positive correlations between its expression and SLEDAI, active lupus nephritis and serum IFN-α levels. In vitro, tRF-3009 over-expressing CD4⁺ T cell profiling and putative analysis linked this product to the type I IFN and oxidative phosphorylation (OXPHOS) pathways. Interestingly, IFN-α is capable of inducing ROS and ATP production in CD4⁺ T cells, while knockdown of tRF-3009 reversed this process. Overexpression of tRF-3009 in CD4⁺ T cells alone was sufficient to upregulate OCR, ROS, and ATP production.

Conclusions

Our study is the first to link aberrant tRF expression and SLE. tRF-3009 may participate in metabolic modulation of IFN-α-induced CD4⁺ T cell OXPHOS in lupus.

SUBMITTER: Geng G 

PROVIDER: S-EPMC8278670 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature