Project description:NK cells are a major immune cell in the uterus during pregnancy. IL15 is required for the maturation of these cells, therefore a mutation in the IL15 gene results in a lack of NK cells. In this study, implantation sites were collected from gestational day 9.5 pregnant IL15 deficient or WT Sprague-Dawley Holtzman rats. RNA was collected, and a Clariom S microarray was performed to elucidate differences in gene expression at the developing placenta and uterus between mutants and WT dams.
Project description:Rhesus macaques vaccinated by rhesus cytomegalovirus vectors expressing simian immunodeficiency virus proteins (RhCMV/SIV) activate gene expression signature associated with IL15. To examine the gene expression signature activated by IL15, we performed longitudinal examinations of rhesus macaques during IL15 treament.
Project description:IL15 has been suggested to reduce WAT mass in obese mice models. However, the underlying molecular mechanism is largely unknown. We determined the gene expression profile of human adipocytes treated with vehicle or IL15. Adipocytes isolated from healthy donors exhibited reduced expression of gene signatures related to adipogenesis and fatty Acid metabolism upon IL15 stimulation, which is consistent with the previous notion that IL15 exhibits an anti-obesity effect. Taken together, our findings suggested that SNORD46 physically interact with IL15 and acts as a natural IL15 antagonist in the serum of donors with obesity to hinder the anti-obese effect of IL15.
Project description:We report gene expression profiles of macrophage and multinucleated cells programmed by IL15 including the mRNAs isolated, libraries prepared and gene expression profiles determined by RNA-seq.
Project description:Half of the patients with high-risk neuroblastoma (NB) who receive GD2-targeted monoclonal antibody do not achieve long-term remissions. Recently, the antibody hu14.18 has been linked to interleukin (IL)2 (hu14.18-IL2) to enhance its efficacy and shown promising preclinical and clinical activity. We developed two new immunocytokines (ICs) by linking two other γc cytokines, IL15 and IL21, to hu14.18. The purpose of this study was to compare hu14.18-IL15 and -IL21 to hu14.18-IL2 in their ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC) against NB. We assessed ADCC of hu14.18-IL15 and -IL2 (human cytokines, cross-reactive to mouse) against GD2low and GD2high NB cell lines in vitro. T-cell deficient mice with orthotopic patient-derived xenografts (PDXs) and immunocompetent mice with transplantable orthotopic NB were used to test all three ICs, including hu14.18-IL21 (murine IL21, not cross-reactive to human). Mechanistic studies were performed using single-cell RNA-sequencing (scRNA-seq). Hu14.18-IL15 and hu14.18-IL2 mediated equivalent in vitro ADCC by human NK cells. When combined with chemotherapy, all three ICs similarly controlled the growth of PDXs in nude mice with murine NK effector cells. However, hu14.18-IL15 and -IL21 outperformed hu14.18-IL2 in immunocompetent mice with syngeneic NB, inducing complete tumor regressions and extending survival. scRNA-seq data revealed an increase in CD8+ T cells and M1 tumor-associated macrophages and decreased regulatory T cells and myeloid-derived suppressor cells in the tumor microenvironment. Hu14.18-IL15 and Hu14.18-IL21 exhibit robust preclinical activity, warranting further consideration for clinical testing in patients with GD2-expressing NB.
Project description:Nonalcoholic steatohepatitis (NASH) is an aggressive liver disease threatening public health, however its natural history is poorly understood. Unlike ob/ob mice, Lep∆I14/∆I14 rats develop unique NASH phenotype with an inflection point of inflammation at postnatal week 16. Using Lep∆I14/∆I14 rats, we studied the natural history of NASH progression by performing an integrated analysis of hepatic transcriptome from postnatal week 4 to 48. Leptin deficiency leads to the precipitously increasing expression of genes encoding rate-limiting enzymes in lipid metabolism. However, hepatic inflammation related genes, pathways and immune-cell infiltration are restricted after week 16, implying an essential role of LEPTIN in regulating hepatic inflammation. Lep∆I14/∆I14 rats share more genes with NASH patients than known mouse models, therefore will provide a better genetic platform for studying NASH than mice.
Project description:The model rats of Yang deficiency syndrome were established by gavage of Huanglian and Dahuang and exhaustive swimming. The rats were treated with Fuzi, Yinfupian and Yangfupian. The liver tissue proteins were extracted and analyzed by TMT proteomics.
Project description:Proteomic analysis was conducted on gastric and duodenal tissues from rats with functional dyspepsia of spleen deficiency and normal rats, as well as rats with functional dyspepsia treated with Jianwei Xiaoshi tablets.
Project description:Iron deficiency occurs when iron demands chronically exceed intake, and is particularly prevalent in pregnant women. Iron deficiency during pregnancy poses health risks for the baby. The placenta serves as the interface between a pregnant mother and her baby; thus, maternal iron deficiency may indirectly impact fetal growth and development by altering placental function. In this study, pregnant Sprague-Dawley rats were fed either a low-iron or iron-replete diet starting two weeks before mating. On gestational day 18.5, RNA was collected, and a Clariom S microarray was performed to elucidate differences in gene expression between gestaional day 18.5 placentas isolated from dams fed iron replete or iron deficient diets.