Interferon-α exacerbates neuropsychiatric phenotypes in lupus-prone mice

BACKGROUND: Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied. METHODS: An intravenous injection of Adv-IFN-α (10 mice, 10 × 10(9) vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 10(9) vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour. RESULTS: In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression. CONCLUSIONS: Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1985-9) contains supplementary material, which is available to authorized users.