Application of regulatory T cells (Tregs) in transplantation, autoimmunity and allergy has been extensively explored, but how Foxp3 and Treg stability is regulated in vivo is incompletely understood. Here, we identify a requirement for Deltex1 (DTX1), a contributor to T-cell anergy and Foxp3 protein level maintenance in vivo. Dtx1−/− Tregs are as effective as WT Tregs in the inhibition of CD4+CD25− T-cell activation in vitro. However, the suppressive ability of Dtx1−/− Tregs is greatly impaired in vivo. We find that Foxp3 expression is diminished when Dtx1−/− Tregs are co-transferred with effector T cells in vivo. DTX1 promotes the degradation of HIF-1α. Knockout of HIF-1α restores the Foxp3 stability and rescues the defective suppressive activity in Dtx1−/− Treg cells in vivo. Our results suggest that DTX1 exerts another level of control on Treg stability in vivo by sustaining the expression of Foxp3 protein in Tregs.

Cellular FLIP (c-FLIP) specifically inhibits caspase-8 and suppresses death receptor–induced apoptosis. c-FLIP has also been reported to transmit activation signals. In this study, we report a novel function of c-FLIP involving inhibition of myeloid cell activation through antagonizing the selective innate signaling pathway. We found that conditional knockout of c-FLIP in dendritic cells (DCs) led to neutrophilia and splenomegaly. Peripheral DC populations, including CD11b+ conventional DCs (cDCs), CD8+ cDCs, and plasmacytoid DCs, were not affected by c-FLIP deficiency. We also found that c-FLIP knockout cDCs, plasmacytoid DCs, and bone marrow–derived DCs (BMDCs) displayed enhanced production of TNF-α, IL-2, or G-CSF in response to stimulation of TLR4, TLR2, and dectin-1. Consistent with the ability of c-FLIP to inhibit the activation of p38 MAPK, the enhanced activation of c-FLIP–deficient BMDCs could be partly linked to an elevated activation of p38 MAPK after engagement of innate receptors. Increased activation was also found in c-FLIP+/− macrophages. Additionally, the increased activation in c-FLIP–deficient DCs was independent of caspase-8. Our results reveal a novel inhibitory role of c-FLIP in myeloid cell activation and demonstrate the unexpected anti-inflammatory activity of c-FLIP. Additionally, our observations suggest that cancer therapy targeting c-FLIP downregulation may facilitate DC activation and increase T cell immunity.

grasp of the underlying science. This situation has changed greatly with our growing understanding of nanoscience, particularly with regard to the role of size effects. Indeed, owing to quantum confinement and surface effects, material properties begin to differ from the bulk at a length scale below ≈100 nm. [2] These effects can impact the electronic, thermal, chemical, and optical properties of a material at the nanoscale. The study of nanocrystals is the driving force behind innovations in electronic, [1,3] optoelectronic, [4,5] and nanophoto nic [6] devices. In addition, nanocrystals are used for catalysis [7,8] and medical applications. [9,10] Nanostructures and nanocrystals are usually fabricated by well-known top-down or bottom-up approaches. [2,[11][12][13] In this contribution, we focus on a distinct third method to create nanocrystalline structures, which combines aspects of those two approaches. Our method utilizes the self-assembly of nanocrystalline structures through thinfilm agglomeration. [14,15] Applying recent developments in epitaxial growth and liftoff of thin films to form membranes, it presents a general framework for achieving self-assembly. The agglomeration achieved by an architectured dewetting process will be described in the following discussion.In the process of annealing a thin film deposited on a substrate, a variety of mass transport phenomena such as surface diffusion, intermixing, evaporation, and condensation may take place (Figure 1). Mass transport occurring on the edge of a film can retract the film to minimize the total surface energy. This process reduces the coverage of the substrate by the film and eventually forms islands of material resting on the substrate. [14,[16][17][18] This inherent ability of thin films to dewet on surfaces and to agglomerate into islands is leveraged to form crystalline nanoparticles to fabricate catalysis [19][20][21][22] as well as electronic [23,24] and nanophotonic devices. [25][26][27][28] This process provides a way to achieve high-throughput nanofabrication [25] of highly oriented and faceted nanostructures that are not obtainable with traditional lithography and etching methods. [29][30][31][32][33][34][35] Dewetting has been studied extensively, both theoretically and experimentally, in single-crystal configurations of elements [31,32,[36][37][38] such as palladium, [39] nickel, [38,40] and silicon, [18,30] which has yielded a detailed understanding of The exploration of crystalline nanostructures enhances the understanding of quantum phenomena occurring in spatially confined quantum matter and may lead to functional materials with unforeseen applications. A novel route to fabricating nanocrystalline oxide structures of exceptional quality is presented. This is achieved by utilizing a self-assembly process of ultrathin membranes composed of the desired oxide. The thermally induced self-assembly of nanocrystalline structures is driven by dewetting the oxide membranes once they are lifted off and transferred onto sapphire surfaces. In thr...