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IRF4 is the pioneer factor for effector T cell maturation. Here we investigated the function of IRF4 in maintaining OX40-related T cell responses following alloantigen activation in a mouse heart transplantation model. Irf4 flox/flox mice were bred with Ox40 cre/+ mice to generate Irf4 flox/flox Ox40 cre/+ mice. Wild type C57BL/6, Irf4 flox/flox Ox40 cre/+ mice were transplanted with BALB/c heart allografts, with or without BALB/c skin-sensitization. CD4+ TEa T cells co-transfer experiments and flow cytometric analysis were conducted to investigate the amount of CD4+ T cells and the percentage of the T effector subset. Irf4 flox/flox Ox40 cre/+ and Irf4 flox/flox Ox40 cre/+ TEa mice were constructed successfully. IRF4 ablation in activated OX40-mediated alloantigen specific CD4+ TEa T cells reduced effector T cell differentiation (CD44hiCD62Llo, Ki67, IFN-γ), which caused long-term allograft survival (> 100 d) in the chronic rejection model. In the donor skin-sensitized heart transplantation model, the formation and function of alloantigen-specific memory CD4+ TEa cells were also impaired in Irf4 flox/flox Ox40 cre/+ mice. Additionally, deletion of IRF4 after T cell activation in Irf4 flox/flox Ox40 cre/+ mice reduced T cell reactivation in vitro. IRF4 ablation after OX40-related T cell activation could reduce effector and memory T cell formation and inhibit their function in response to alloantigen stimulation. These findings could have significant implications in targeting activated T cells to induce transplant tolerance. • Irf4 flox/flox Ox40 cre/+ and Irf4 flox/flox Ox40 cre/+ TEa mice was successfully constructed. • Ox40-specific IRF4 knockout prevented chronic rejection and secondary response in mice heart transplantation. • IRF4 was needed after OX40 related-T cell priming for antigen-specific effector and memory T cell responses. • Ablation of IRF4 after T cell activation in Irf4 flox/flox Ox40 cre/+ mice also reduced T cell reactivation in vitro. [ABSTRACT FROM AUTHOR]

Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin–Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7−/− mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection. Schematic of the role of P2X7 receptor in neomycin-induced HC loss. Under physiological control conditions, P2X7 receptor acts as a channel. ATP and small molecules can pass through it, while large molecules cannot. After neomycin exposure, large amounts of ATP are released from cells and the extracellular concentration of ATP increases rapidly. In addition, more P2X7 receptors are synthesized and appear in the membrane. The high concentrations of ATP cause P2X7 receptor to open as a pore that is large enough for neomycin to enter the HCs, thus damaging the HCs and causing apoptosis. [Display omitted] • AGAs induced cochlear HC damage is associated with changes in eATP concentration and P2X7 receptor activation. • P2X7 receptor is involved to AGAs uptake in HCs. • AGAs-related mitochondria-mediated oxidative stress could be abolished by deleting P2rx7. • P2X7 receptor might be a new target for HC protection from AGAs. [ABSTRACT FROM AUTHOR]

Style transfer has been widely applied in the fashion industry for design assistance. This paper focuses on object-level image style transfer for specific texture regions on fashion images. The current methods mostly utilize extra conditional inputs to obtain regions of interest in fashion images, which take extensive time and cost to prepare these data. To address this issue, we propose a two-stage unsupervised approach named TsrNet for clothing texture style transfer between images. Firstly, we construct a network named Mask-GAN to unsupervisedly split out the clothing texture region. Secondly, we improve CycleGAN to interchange the texture on specific target regions of the two images. Specifically, considering the diversity of fashion texture, we construct a multiscale module (Drf-module) with dynamic perceptual fields and design an image gradient-based texture structure loss (GTS) to perform texture transfer. Qualitative and quantitative experimental results show the effectiveness of our algorithm for clothing-specific region style transfer. • A novel two-stage framework is proposed for garments region-specific style transfer. • The Mask-GAN is proposed for target region extraction in a self-supervised manner. • A multi-scale module with dynamic receptive field is built to generate various styles. • A texture structure loss is built to make the generated styles satisfy human vision. [ABSTRACT FROM AUTHOR]