Project description:Microglia activation is a hallmark in Alzheimer Disease. Non-active and Active microglia were isolated from young and aged WT mice and before- and after- pathology mouse models of Alzheimer Disease. Microarray analysis was used to determine the global gene expression programe in microglia during pathological (Abeta or TAU pathology) versus control state.
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects 20-150 out of 100,000 people globally. Reactive oxygen species (ROS) generation from mitochondrial dysfunction contributes to risk for SLE and autoimmune states and are potential targets for the treatment of autoimmunity. HRES-1/Rab4 (Rab4A) is a GTPase linked to mitochondrial oxidative stress and activation of the mechanistic target of rapamycin (mTOR), and has been linked to SLE pathogenesis. Here, RNA-sequencing (RNA-seq) was used to examine the expression of different classes of splenocytes (CD4+, CD8+, CD19+) from the lupus-prone SLE1.2.3. triple-congenic (B6.TC) mouse, as well as Rab4AQ72L mutant mice (which exhibits constitutive overexpression of Rab4a), and mice with CD4 T cell-specific deletion of Rab4A (KO).
Project description:Previous studies showed that bone marrow derived-mesenchymal stem cells (BMMSCs) from patients with systemic lupus erythematosus (SLE) and lupus animal models have deficiency in their capacities of proliferation, differentiation, secretion of cytokines and other functions. In this study, we aim to investigate the different gene patterns of BMMSCs between normal and SLE individuals using genome-scale DNA microarrays. We found that among all the genes investigated in microarray slides, a total of 1, 905 genes were differentially expressed by BMMSCs SLE patients, in which 652 genes were up-regulated and 1253 genes were down-regulated. Gene ontology analysis showed that the majority of these genes were related to cell cycle and protein binding. Pathway analysis showed that differentially regulated signal pathways involved actin cytoskeleton, focal adhesion, tight junction and TGF-β pathway. Our data suggested that there were differential gene expression patterns of BMMSCs between normal and SLE individuals, and further studies are needed to reveal the mechanisms for such differences. Bone marrow (BM) was obtained from 4 patients with SLE and 4 normal controls. BMMSCs were cultured and mRNA was extracted. Standard human reference RNA were purchased. Every slide: SLE or normal vs control, then SLE vs normals.
Project description:Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. To reveal the heterogeneity in the pathogenesis of SLE between male and female patients. PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.
Project description:Mature neutrophis were freshly isolated from blood of pediatric systemic lupus erythematosus (SLE) patients and healthy donors. Illumina microarray was used to assess transcriptional changes between SLE group and Control group. To uderstand further the gene expression difference between SLE and healthy neutrofils, neutrophils from healthy donors were cultured with autologous sera, SLE sera or Interferon and microarray data was used to compare with fresh SLE neutrophils.
Project description:Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Microglia control synaptic pruning during early postnatal brain development. The process in NPSLE remains unclear. Here, we show that microglia-coordinated elimination of synaptic terminals participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We elucidated that lupus mice developed increased depression- and anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. Microglial engulfment of synapses explained behavioral disorders. To elucidate the mechanism of synaptic pruning by microglia, we sequenced the gene expression in sorted microglia from both lupus (MRL/lpr) mice and the wild-type (MRL/mpj) controls.
Project description:Mature neutrophis were freshly isolated from blood of pediatric systemic lupus erythematosus (SLE) patients and healthy donors. Illumina microarray was used to assess transcriptional changes between SLE group and Control group. To uderstand further the gene expression difference between SLE and healthy neutrofils, neutrophils from healthy donors were cultured with autologous sera, SLE sera or Interferon and microarray data was used to compare with fresh SLE neutrophils. (Expt 1) Neutrophils from 21 SLE samples (19 patients) and 12 healthy donors were isolated, and extracted RNAs were used generate microarray data. (Expt 2) Neutrophils isolated from 2 healthy children (not used in the first experiment) were cultured with autologous sera (control), Interferon alpha (100U and 1000U), and 4 SLE sera and 6 SLE sera for 6 hours and RNAs were extract for microarray experiment.
Project description:Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE) and significantly contributes to morbidity and mortality. To date, no pharmacologic intervention has shown to reduce CV risk in SLE. Dysregulation of innate immune responses, including aberrant type I-Interferon (IFN)-neutrophil interactions, has been proposed to significantly contribute to enhanced CV risk in SLE. In lupus animal models, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We hypothesized that JAK/STAT inhibition in SLE subjects would result in amelioration of cardiometabolic and immunologic parameters previously associated with enhanced CVD risk.