Project description:We examined the brain's choroid plexus and myeloid cell populations isolated from the brain of 5XFAD Alzheimer's disease transgenic mice following PD-1 blockade
Project description:Microglia and monocyte-derived macrophages (MDM) are key players in coping with Alzheimer's disease (AD). In amyloidosis mouse models, activation of microglia was found to be TREM2-dependent. Here, using Trem2-/-5xFAD mice, we assessed whether MDM act via a TREM2-dependent pathway. We adopted a treatment protocol targeting the programmed cell death ligand-1 (PD-L1) immune checkpoint, previously shown to modify AD via MDM involvement. Blocking PD-L1 in Trem2-/-5xFAD mice resulted in cognitive improvement and reduced levels of water-soluble amyloid beta (Aβ)1-42 with no effect on amyloid plaque burden. Single-cell RNA sequencing revealed that MDM, derived from both Trem2-/- and Trem2+/+5xFAD mouse brains, express a unique set of genes encoding scavenger receptors (e.g. Mrc1, Msr1). Blocking monocytes trafficking using anti-CCR2 antibody completely abrogated the cognitive improvement induced by anti-PD-L1 in Trem2-/-5xFAD mice, and similarly but to lower extent in Trem2+/+5xFAD mice. These results highlight a TREM2-independent disease-modifying activity of MDM in amyloidosis mouse model.
Project description:Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that work by targeting molecules on immune cells that can inhibit the immune system's ability to attack cancer cells. One such checkpoint molecule is PD-1, which is found on the surface of T cells (a type of immune cell) and helps to prevent them from attacking healthy cells. When PD-1 binds to its ligand (a molecule on the surface of some cells), it sends a signal to the T cell to \\"turn off\\" and not attack the cell. This mechanism is important in preventing the immune system from attacking healthy cells, but it can also be exploited by cancer cells to avoid detection and destruction by the immune system. In this study YUMM2.1 mouse tumour cells were implanted subcutaneously. The effect of IFN-γ-pre-treatment, PARP14 inhibition and PD-1 antibody treatment are reported by RNA-seq.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:The aim of this study was to assess whether chronic treatment with RPV can modulate the progression of chronic liver disease, especially of non-alcoholic fatty liver disease (NAFLD), through a nutritional model in wild-type mice Mice were daily treated with RPV (p.o.) and fed with normal or high fat diet during 3 months to induce fatty liver disease
Project description:Cancer treatment has been revolutionized by immune checkpoint inhibitors, which regulate immune cell function by blocking the interactions between immune checkpoint molecules and their ligands. The interaction between programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) is a target for immune checkpoint inhibitors. Nanobodies, which are recombinant variable domains of heavy-chain-only antibodies, can replace existing immune checkpoint inhibitors, such as anti-PD-1 or anti-PD-L1 conventional antibodies. However, the screening process for high-affinity nanobodies is laborious and time-consuming. Here, we identified high-affinity anti-PD-1 nanobodies using peptide barcoding, which enabled reliable and efficient screening by distinguishing each nanobody with a peptide barcode that was genetically appended to each nanobody. We prepared a peptide-barcoded nanobody (PBNb) library with thousands of variants. Three high-affinity PBNbs were identified from the PBNb library by quantifying the peptide barcodes derived from high-affinity PBNbs. Furthermore, these three PBNbs neutralized the interaction between PD-1 and PD-L1. Our results demonstrate the utility of peptide barcoding and the resulting nanobodies can be used as experimental tools and antitumor agents. Peptide barcoding can be used to screen for molecules other than nanobodies. Our methods, such as the design of peptide barcodes, the design of peptide-barcoded molecules, preparation of peptide-barcoded molecule library, and quantification of peptide barcodes, are helpful in screening for peptide-barcoded molecules.
