The transcription factor Friend leukemia integration 1 (Fli-1) regulates the expression of numerous cytokines and chemokines and alters the progression of lupus nephritis in humans and in the MRL/MpJ-Fas lpr (MRL/lpr) mouse model. Th17-mediated immune responses are notably important as they promote ongoing inflammation. The purpose of this study is to determine the impact of Fli-1 on expression of interleukin-17A (IL-17A) and the infiltration of immune cells into the kidney. IL-17A concentrations were measured by ELISA in sera collected from MRL/lpr Fli-1-heterozygotes (Fli-1 +/− ) and MRL/lpr Fli-1 +/+ control littermates. Expression of IL-17A and related proinflammatory mediators was measured by real-time polymerase chain reaction (RT-PCR). Immunofluorescence staining was performed on renal tissue from MRL/lpr Fli-1 +/− and control littermates using anti-CD3, anti-CD4, and anti-IL-17A antibodies to detect Th17 cells and anti-CCL20 and anti-CD11b antibodies to identify CCL20 + monocytes. The expression of IL-17A in renal tissue was significantly reduced; this was accompanied by decreases in expression of IL-6, signal transducer and activator of transcription 3 (STAT3), and IL-1β. Likewise, we detected fewer CD3 + IL-17 + and CD4 + IL-17 + cells in renal tissue of MLR/lpr Fli-1 +/− mice and significantly fewer CCL20 + CD11b + monocytes. In conclusion, partial deletion of Fli-1 has a profound impact on IL-17A expression and on renal histopathology in the MRL/lpr mouse.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs, including the central nervous system. Neuropsychiatric SLE (NPSLE) is a severe and potentially fatal condition. Several factors including autoantibodies have been implicated in the pathogenesis of NPSLE. However, definitive biomarkers of NPSLE are yet to be identified owing to the complexity of this disease. This is a major barrier to accurate and timely diagnosis of NPSLE. Studies have identified several autoantibodies associated with NPSLE ; some of these autoantibodies are well investigated and regarded as symptomspecific. In this review, we discuss recent advances in our understanding of the manifestations and pathogenesis of NPSLE. In addition, we describe representative symptomspecific autoantibodies that are considered to be closely associated with the pathogenesis of NPSLE.

Transcription factors E26 transformation-specific-1 (Ets-1) and Friend leukemia insertion site-1 (Fli-1) and type I interferon (IFN) have been implicated in systemic lupus erythematosus (SLE). We examined the expression of these genes in peripheral blood mononuclear cells (PBMCs) from Japanese patients with SLE and analyzed their association with SLE. We enrolled 53 Japanese patients with SLE, 42 patients with rheumatoid arthritis (RA), and 30 healthy donors (HDs) (as controls) in this study. PBMCs were collected from all participants, and the expressions of Ets-1, Fli-1, and three interferon-inducible genes (IFIGs) (interferon-inducible protein with tetratricopeptide 1 [IFIT1], interferon-inducible protein 44 [IFI44], and eukaryotic translation initiation factor 2 alpha kinase 2 [EIF2AK2]) were measured using real-time polymerase chain reaction (PCR). The relationships of each molecule with clinical symptoms, laboratory data, and treatments were analyzed. The expression of Ets-1 and Fli-1 was significantly lower in the PBMCs from patients with SLE than that in the PBMCs from patients with RA and HDs. The expression of the three IFIGs was significantly higher in the PBMCs from patients with SLE than that in the PBMCs from patients with RA and HDs. For patients with SLE, significantly positive correlations were found between Ets-1 and three IFIGs; a similar trend was observed between Fli-1 and IFIGs. IFIG expression in the PBMCs was significantly higher in patients with SLE than that in other participants, and the expression of Ets-1 and Fli-1 was positively associated with IFN expression. Therefore, it was suggested that Ets-1 and Fli-1 were associated with the pathophysiology of SLE by regulating the type I IFN pathway.

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.