CD4 T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4 T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction. In the absence of IRF4, chromatin accessibility and binding of Helios at PD-1 cis-regulatory elements were increased, resulting in enhanced PD-1 expression and CD4 T cell dysfunction. The dysfunctional state of Irf4-deficient T cells was initially reversible by PD-1 ligand blockade, but it progressively developed into an irreversible state. Hence, IRF4 controls a core regulatory circuit of CD4 T cell dysfunction, and targeting IRF4 represents a potential therapeutic strategy for achieving transplant acceptance.
An understanding of the viscoelastic properties of molecularly thin lubricant film is essential to clarify tribological issues of head-disk interface (HDI) in high-density recording hard disk drives. Characteristic conditions for the HDI occur when lubricant molecules are extremely confined in the gap between the head and the disk surfaces, and the surfaces slide at high speeds. The lower the flying height, the more this confinement affects the flying characteristics. However, a few attempts have been made at clarifying the dynamic viscoelastic properties of confined lubricant molecules. This is because a method of measuring the dynamic shear force has not yet been established. Fiber wobbling method enables us to measure the shear force with a detection limit of less than 1 nN. Additionally, frequency of shear can be set at several kHz. Further, the gap which confines the lubricant is controlled with a resolution of 0.1 nm. Using the FWM, we investigated the effect that confinement had on the dynamic viscoelastic properties of perfluoropolyether lubricants on a magnetic disk. We found that the viscosity started to increase at a gap width that was less than a few hundred nanometers, which is hundreds of times larger than the molecular size. On the other hand, elasticity suddenly appeared at a gap width that was less than a few nanometers, which is equivalent to a few molecular sizes. Both the viscosity and elasticity increased monotonically as the gap decreased.
Since December 2019, the ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly affected solid organ transplantation (SOT) worldwide and has become a threat to the lives of SOT recipients. Here, we have reviewed, condensed, and organized the available information on COVID-19 to provide recommendations to transplant healthcare workers. Our review of reported cases shows that the symptoms of SOT patients with COVID-19 are similar to those of the normal population, but their severity and outcomes are worse. Thus far, there is no evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly causes permanent damage to kidney, liver, or heart allografts.
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