ObjectiveMicroRNA have recently been identified as regulators that modulate target gene expression and are involved in shaping the immune response. This study was undertaken to investigate the contribution of microRNA‐146a (miR‐146a), which was identified in the pilot expression profiling step, to the pathogenesis of systemic lupus erythematosus (SLE).MethodsTaqMan microRNA assays of peripheral blood leukocytes were used for comparison of expression levels of microRNA between SLE patients and controls. Transfection and stimulation of cultured cells were conducted to determine the biologic function of miR‐146a. Bioinformatics prediction and validation by reporter gene assay and Western blotting were performed to identify miR‐146a targets.ResultsProfiling of 156 miRNA in SLE patients revealed the differential expression of multiple microRNA, including miR‐146a, a negative regulator of innate immunity. Further analysis showed that underexpression of miR‐146a negatively correlated with clinical disease activity and with interferon (IFN) scores in patients with SLE. Of note, overexpression of miR‐146a reduced, while inhibition of endogenous miR‐146a increased, the induction of type I IFNs in peripheral blood mononuclear cells (PBMCs). Furthermore, miR‐146a directly repressed the transactivation downstream of type I IFN. At the molecular level, miR‐146a could target IFN regulatory factor 5 and STAT‐1. More importantly, introduction of miR‐146a into the patients' PBMCs alleviated the coordinate activation of the type I IFN pathway.ConclusionThe microRNA miR‐146a is a negative regulator of the IFN pathway. Underexpression of miR‐146a contributes to alterations in the type I IFN pathway in lupus patients by targeting the key signaling proteins. The findings provide potential novel strategies for therapeutic intervention.

The brookite phase of TiO(2) is hardly prepared and rarely studied in comparison with the common anatase and rutile phases. In addition, there exist immense controversies over the cognition of the light-induced liveliness of this material. Here, a novel, low-basicity solution chemistry method was first used to prepare homogeneous high-quality brookite TiO(2) single-crystalline nanosheets surrounded with four {210}, two {101}, and two {201} facets. These nanosheets exhibited outstanding activity toward the catalytic degradation of organic contaminants superior even to that of Degussa P25, due to the exposure of high-energy facets and the effective suppression of recombination rates of photogenerated electrons and holes by these facets as the oxidative and reductive sites. In contrast, irregularly faceted phase-pure brookite nanoflowers and nanospindles were inactive in catalytic reactions. These results demonstrate that the photocatalytic activity of brookite TiO(2) is highly dependent upon its exposed facets, which offers a strategy for tuning the catalysts from inert to highly active through tailoring of the morphology and surface structure.

The recent discovery of microRNAs (miRNAs) has revealed a new layer of gene expression regulation, affecting the immune system. Here, we identify their roles in regulating human plasmacytoid dendritic cell (PDC) activation. miRNA profiling showed the significantly differential expression of 19 miRNAs in PDCs after Toll-like receptor 7 (TLR7) stimulation, among which miR-155* and miR-155 were the most highly induced. Although they were processed from a single precursor and were both induced by TLR7 through the c-Jun N-terminal kinase pathway, miR-155* and miR-155 had opposite effects on the regulation of type I interferon production by PDC. IntroductionPlasmacytoid dendritic cell (PDC) is a distinct dendritic cell type, specialized for the rapid secretion of type I interferon (type I IFN) in response to viruses. [1][2][3] It has been demonstrated that PDCs can coordinate events during the course of viral infection, autoimmune diseases, and cancer. PDCs, through their production of interferon-␣ (IFN-␣) and other cytokines, and through antigen presentation, link the innate and adaptive immune responses. 3 PDC deficiency, leading to low levels of IFN-␣ production, results in an inadequate immune response, entailing susceptibility to viral infections or cancer, whereas excessive secretion of IFN-␣ can induce hyperimmune activation, which may lead to autoimmune disease or, in the case of HIV infection, CD4 ϩ T-cell death. [2][3][4][5] Therefore, type I IFN production by PDCs must be under tight control to prevent improper immune responses, which could be harmful to the host. 2,3 PDCs express high levels of Toll-like receptor 7 (TLR7) and TLR9. The interaction between TLR7/9 and their ligands leads to the activation of the myeloid differentiation primary response gene 88/IL-1/4 receptor-associated kinase/tumor necrosis factor (TNF) receptor-associated factor 6/IB kinases (MyD88/IRAK1/4/TRAF6/ IKKs) pathway and the subsequent phosphorylation of interferonregulatory receptor 7 (IRF-7), which is translocated into the nucleus and initiates IFN-␣ transcription. 2,6 The phosphatidylinositol 3-kinase/Av-akt murine thymoma viral oncogene homolog 1/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway and p38 mitogen-activated protein kinase (MAPK) activity have also been shown to positively regulate type I IFN production. 7,8 In contrast to these positive regulators, an array of surface receptors on PDCs, such as blood dendritic cell antigen 2 (BDCA2), dendritic cell immunoreceptor (DCIR), immunoglobulin-like transcript 7 (ILT7), high-affinity immunoglobulin E receptor (Fc⑀RI), and natural killer partner 44 (NKp44), are reported to signal through a powerful immunoreceptor tyrosine-based activation motif (ITAM)-mediated, B-cell receptor (BCR)-like regulatory pathway to counter-regulate the prominent TLR signaling pathway. 2,9-13 Although the kinetics of type I IFN production by human PDCs have been investigated in detail, 14 the dynamic regulatory mechanism has not yet been clarified. Both TLR7 and TLR9 are considered closely ...