CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1–4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7–10. Herein, we show that Th17 differentiation can occur in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+ Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 without TGF-β1 were pathogenic in this disease model. These data suggest an alternative mode for Th17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore have may have therapeutic implications.

A lightweight, flexible, and highly efficient energy management strategy is needed for flexible energy-storage devices to meet a rapidly growing demand. Graphene-based flexible supercapacitors are one of the most promising candidates because of their intriguing features. In this report, we describe the use of freestanding, lightweight (0.75 mg/cm(2)), ultrathin (<200 μm), highly conductive (55 S/cm), and flexible three-dimensional (3D) graphene networks, loaded with MnO(2) by electrodeposition, as the electrodes of a flexible supercapacitor. It was found that the 3D graphene networks showed an ideal supporter for active materials and permitted a large MnO(2) mass loading of 9.8 mg/cm(2) (~92.9% of the mass of the entire electrode), leading to a high area capacitance of 1.42 F/cm(2) at a scan rate of 2 mV/s. With a view to practical applications, we have further optimized the MnO(2) content with respect to the entire electrode and achieved a maximum specific capacitance of 130 F/g. In addition, we have also explored the excellent electrochemical performance of a symmetrical supercapacitor (of weight less than 10 mg and thickness ~0.8 mm) consisting of a sandwich structure of two pieces of 3D graphene/MnO(2) composite network separated by a membrane and encapsulated in polyethylene terephthalate (PET) membranes. This research might provide a method for flexible, lightweight, high-performance, low-cost, and environmentally friendly materials used in energy conversion and storage systems for the effective use of renewable energy.

SUMMARY Systemic infusion of bone marrow mesenchymal stem cells (BMMSCs) shows therapeutic benefit for a variety of autoimmune diseases, but the underlying mechanisms are poorly understood. Here we show that in mice systemic infusion of BMMSCs induced transient T-cell apoptosis via the Fas ligand (FasL)-dependent Fas pathway and could ameliorate disease phenotypes in fibrillin-1 mutated systemic sclerosis (SS) and dextran sulfate sodium-induced experimental colitis. FasL−/− BMMSCs did not induce T-cell apoptosis in recipients, and could not ameliorate SS and colitis. Mechanistic analysis revealed that Fas-regulated monocyte chemotactic protein 1 (MCP-1) secretion by BMMSCs recruited T-cells for FasL-mediated apoptosis. The apoptotic T-cells subsequently triggered macrophages to produce high levels of TGFβ which in turn led to the upregulation of Tregs and, ultimately, to immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via Fas/FasL to induce T-cell apoptosis.