Data_Sheet_1_Identification of Renal Long Non-coding RNA RP11-2B6.2 as a Positive Regulator of Type I Interferon Signaling Pathway in Lupus Nephritis.docx
Objective: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Type I interferon (IFN-I) is associated with the pathogenesis of LN. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of SLE, however, the roles of lncRNAs in LN are still poorly understood. Here, we identified and investigated the function of LN-associated lncRNA RP11-2B6.2 in regulating IFN-I signaling pathway.
Methods: RNA sequencing was used to analyze the expression of lncRNAs in kidney biopsies from LN patients and controls. Antisense oligonucleotides and CRISPRi system or overexpression plasmids and CRISPRa system were used to perform loss or gain of function experiments. In situ hybridization, imaging flow cytometry, dual-luciferase reporter assay, and ATAC sequencing were used to study the functions of lncRNA RP11-2B6.2. RT-qPCR, ELISA, and western blotting were done to detect RNA and protein levels of specific genes.
Results: Elevated lncRNA RP11-2B6.2 was observed in kidney biopsies from LN patients and positively correlated with disease activity and IFN scores. Knockdown of lncRNA RP11-2B6.2 in renal cells inhibited the expression of IFN stimulated genes (ISGs), while overexpression of lncRNA RP11-2B6.2 enhanced ISG expression. Knockdown of LncRNA RP11-2B6.2 inhibited the phosphorylation of JAK1, TYK2, and STAT1 in IFN-I pathway, while promoted the chromatin accessibility and the transcription of SOCS1.
Conclusion: The expression of lncRNAs is abnormal in the kidney of LN. LncRNA RP11-2B6.2 is a novel positive regulator of IFN-I pathway through epigenetic inhibition of SOCS1, which provides a new therapeutic target to alleviate over-activated IFN-I signaling in LN.
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity