Plasmacytoid dendritic cells (pDCs) were considered to be the major IFNα source in systemic lupus erythematosus (SLE) but their phenotype and function in different disease status have not been well studied. To study the function and phenotype of pDCs in lupus-prone mice we used 7 strains of lupus-prone mice including NZB/W F1, NZB, NZW, NZM2410, B6.NZMSle1/2/3, MRL/lpr and BXSB/Mp mice and C57BL/6 as control mice. Increased spleen pDC numbers were found in most lupus mice compared to C57BL/6 mice. The IFNα-producing ability of BM pDCs was similar between lupus and C57BL/6 mice, whereas pDCs from the spleens of NZB/W F1 and NZB mice produced more IFNα than pDCs from the spleens of C57BL/6 mice. Furthermore, spleen pDCs from MRL-lpr and NZM2410 mice showed increased responses to Tlr7 and Tlr9, respectively. As the disease progressed, IFN signature were evaluated in both BM and spleen pDC from lupus prone mice and the number of BM pDCs and their ability to produce IFNα gradually decreased in lupus-prone mice. In conclusion, pDC are activated alone with disease development and its phenotype and function differ among lupus-prone strains, and these differences may contribute to the development of lupus in these mice.

Objective. Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Pristane-treated B6 mice develop severe DAH within 2 weeks of treatment. ) is a pleiotropic microRNA that plays a crucial role in the regulation of immune responses. Recent studies have revealed a pathogenic role of miR-155 in various autoimmune disorders. The purpose of this study was to examine the role of miR-155 in the development of DAH in pristane-induced lupus using miR-155-knockout (miR-155 2/2 ) mice and miR-155 antagomir to silence miR-155.Methods. DAH was induced by an intraperitoneal injection of 0.5 ml of pristane. MicroRNA-155 antagomir was administered intravenously to silence miR-155 expression. Lung tissues were collected for RNA extraction and were embedded in paraffin for sectioning. Gene expression profiling data were analyzed using Ingenuity Pathway Analysis. Real-time quantitative polymerase chain reaction analysis was used for single-gene validation. Luciferase reporter assay and argonaute 2 immunoprecipitation were performed for target validation.Results. MicroRNA-155 expression was significantly increased during the development of DAH. Disease progression was reduced in miR-155 2/2 mice as well as by in vivo silencing of miR-155 using a miR-155 antagomir. MicroRNA-155 silencing dampened pristaneinduced ectopic activation of multiple inflammatory pathways and reduced the expression of proinflammatory cytokines. Several negative regulators of NF-kB signaling were inhibited by pristane and were reactivated in miR-155 2/2 mice. In particular, the antiinflammatory factor peroxisome proliferator-activated receptor a was identified as a direct target of miR-155.Conclusion. MicroRNA-155 promotes pristaneinduced lung inflammation. It contributes to ectopic activation of NF-kB signaling pathways by targeting multiple negative regulators. MicroRNA-155 antagomir may be a promising therapeutic strategy for treating acute lung inflammation in lupus.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems. The clinical manifestations in lupus patients vary considerably, ranging from mild skin involvement to critical and life-threatening diseases of internal organs (1). The lungs are commonly affected in SLE, and can develop pleural, parenchymal, vascular, and airway dis-

Preptin, an oligopeptide secreted by pancreatic β‐cell, plays a significant role in glycometabolism and bone metabolism. Preptin strengthens proliferation and differentiation of osteoblasts, but the mechanism is unclear. Here, we explored the role of the Wnt/β‐catenin signaling pathway which is well known to affect bone development and remodelling in the function of preptin. We found that preptin promoted the cell proliferative activity and osteoblastic differentiation in osteoblast‐like MC3T3‐E1 cells in a dose‐independent manner, as evidenced by elevation in osteogenic genes, alkaline phosphatase activity and alizarin red staining in a dose‐independent manner. Additionally, our findings demonstrated that the β‐catenin expression level and runt‐related transcription factor 2, which is the key downstream target of this pathway, were increased. The Wnt/β‐catenin signalling pathway antagonist DKK1 abrogated the proliferative effect and differentiation function of preptin in MC3T3‐E1 cells. These data indicated that preptin may be a potential therapeutic target for the treatment of osteoporosis and that osteogenic impact of preptin in MC3T3‐E1 cells might be mediated by the Wnt/β‐catenin signalling pathway. © 2019 IUBMB Life, 9999(9999):1–9, 2019

T follicular helper (Tfh) cells are crucial for regulating autoimmune inflammation and protective immunity against viral infection. However, the molecular mechanism controlling Tfh cell differentiation is poorly understood. Here, through two mixed bone marrow chimeric experiments, we identified Peli1, a T cell-enriched E3 ubiquitin ligase, as an intrinsic regulator that inhibits Tfh cell differentiation. Peli1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator (ICOS) expression, and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4+ T cells. Mechanistically, increased ICOS expression on Peli1-KO CD4+ T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2, a transcription factor that inhibits Tfh differentiation. Therefore, reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO cells. As a consequence, Peli1-deficient CD4+ T cells promoted lupus-like autoimmunity but protected against H1N1 influenza virus infection in mouse models. Collectively, our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfh-related autoimmunity or infectious diseases.