A5055090130- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Sphingolipid Metabolism and Signaling
- Immune cells in cancer
- Immune Response and Inflammation
- interferon and immune responses
- Immunodeficiency and Autoimmune Disorders
- Monoclonal and Polyclonal Antibodies Research
- Salivary Gland Disorders and Functions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- Pharmacological Effects of Natural Compounds
- Hepatitis Viruses Studies and Epidemiology
- Complement system in diseases
- Parvovirus B19 Infection Studies
- Diabetes and associated disorders
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Cholesterol and Lipid Metabolism
- Nuclear Receptors and Signaling
- Systemic Sclerosis and Related Diseases
Florida College
2015-2024
University of Florida
2014-2024
University of Florida Health Science Center
2024
ENT and Allergy
2021-2024
Peking University
2022
Abstract Objective The premature atherosclerosis seen in patients with systemic lupus erythematosus (SLE) is not explained by traditional risk factors. SLE disease activity, such as renal involvement and presence of autoantibodies, associated elevated serum levels type I interferon (IFN‐I), a family cytokines potent antiviral antiproliferative effects. This study was undertaken to test the hypothesis that IFN‐I could lead endothelial dysfunction, surrogate for cardiovascular disease, causing...
Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg has been challenging. Here, using single-cell RNA sequencing immune from renal clear carcinoma (ccRCC) patients, we identify two distinct transcriptional fates TI cells, Fate-1 Fate-2. The signature is associated with poorer prognosis ccRCC several other solid cancers. CD177, surface protein normally expressed on...
Abstract Introduction More than half of systemic lupus erythematosus (SLE) patients show evidence excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection IFN-I proteins in serum is unreliable, the measurement interferon-stimulated gene (ISG) expression expensive time consuming. The aim this study was to identify surrogate marker for activity clinical samples monitoring response therapy. Methods Monocyte surface Fcγ...
Exercise offers short-term and long-term health benefits, including an increased metabolic rate energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates conversion of white into brown adipocytes as well mitochondrial biogenesis expenditure. Remarkably, irisin is highly expressed myocardium, but its physiological effects the heart are unknown. objective this work to investigate irisin's potential multifaceted on cardiomyoblasts For purpose, H9C2...
Diffuse alveolar hemorrhage (DAH) in lupus patients confers >50% mortality, and the cause is unknown. We undertook this study to examine pathogenesis of DAH C57BL/6 mice with pristane-induced lupus, a model human lupus-associated DAH.Clinical/pathologic immunologic manifestations were compared those humans. Tissue distribution pristane was examined by mass spectrometry. Cell types responsible for disease determined vivo depletion using clodronate liposomes antineutrophil monoclonal...
Most lupus patients produce autoantibodies against small ribonucleoproteins such as Sm/RNP and Ro 60 (containing U1 Y1-Y5 RNAs, respectively). We undertook this study to investigate whether the RNA components of these antigens, which contain extensive tracts single- double-stranded RNA, signatures viral infection, activate innate immunity.U1 Y RNAs were affinity purified from K562 cells. Murine bone marrow-derived dendritic cells (DCs), human HEK 293 cells, murine RAW264.7 stimulated with...
To define the pathogenesis of bone marrow (BM) involvement in systemic lupus erythematosus (SLE).Tumor necrosis factor α (TNFα) levels, cell death, and cellular damage BM from SLE patients, controls, mice with pristane-induced were analyzed using a morphometric technique immunohistochemistry. The abnormalities was studied wild-type (WT), TNFα(-/-) , Toll-like receptor-deficient (TLR-7(-/-) ), interferon (IFN)-α/β/ω receptor-knockout (IFNAR(-/-) B cell-deficient (μmt) treated pristane. Flow...
An effective cancer therapy requires killing cells and targeting the tumor microenvironment (TME). Searching for molecules critical multiple cell types in TME, we identified NR4A1 as one such molecule that can maintain immune suppressive TME. Here, establish a valid target immunotherapy describe first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades within hours vitro exhibits long-lasting degradation tumors with an excellent safety profile....
Abstract Genetic polymorphisms of IFN regulatory factor 5 (IRF5) are associated with an increased risk lupus in humans. In this study, we examined the role IRF5 pathogenesis pristane-induced mice. The pathological response to pristane IRF5−/− mice shared many features type I receptor (IFNAR)−/− and TLR7−/− mice: production anti-Sm/RNP autoantibodies, glomerulonephritis, generation Ly6Chi monocytes, IFN-I all were greatly attenuated. Lymphocyte activation following injection was diminished...
The generation of CD138+ phagocytic macrophages with an alternative (M2) phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X receptor-α (LXRα) oxysterol-regulated transcription factor promotes reverse cholesterol transport and macrophage activation. Conversely, hypoxia-inducible 1-α (HIF1α) classical (M1) objective this study was to see if lupus can be treated by enhancing the M2-like using LXR agonists. Peritoneal pristane-treated mice had M1 phenotype, high...
Objective Peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients exhibit a gene expression program (interferon [IFN] signature) that is attributed to overproduction of type I IFNs by plasmacytoid dendritic cells. Type have been thought play role the pathogenesis SLE. This study was undertaken examine an unexpected influence monocyte/macrophages on IFN signature. Methods Proinflammatory (classic) and antiinflammatory (nonclassic) were sorted from mice...
Abstract Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined cause of impaired apoptotic cell clearance human and murine lupus. accumulated bone marrow from lupus patients but not nonautoimmune undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired uptake MΦ also was seen mice treated i.p. with pristane (develop lupus) mineral oil (MO) (do develop lupus). The inflammatory response both MO rapidly depleted resident...
Abstract Objective Systemic lupus erythematosus (SLE) is associated with type I interferons (IFNs) and can be induced by IFNα treatment. This study looked for evidence of autoimmunity in a pedigree consisting 4 family members balanced translocation 9;21 2 an unbalanced resulting trisomy the short (p) arm part long (q) chromosome 9. These latter subjects had 3 copies IFN gene cluster. Methods Subjects were evaluated clinically serologically autoimmune disease. Expression levels IFNα4, IFNβ,...
Objective Pristane‐induced lupus is associated with nonresolving inflammation and deficiency of proresolving macrophages. Proresolving nonclassic macrophages ( NCM s) are less responsive to type I interferon IFN ) than classic CM s; which proinflammatory), reflecting their relative expression levels the receptor IFNAR ). This study was undertaken investigate regulation in Methods We carried out gene profiling purified s from mice treated pristane (which develop lupus) or mineral oil...
Background: Pristane-treated mice chronically produce high levels of anti-ribonucleoprotein/Smith (anti-Sm/RNP) and other lupus autoantibodies.The present study addressed how these autoantibody are maintained over time.Methods: Lupus was induced in BALB/c using pristane.Naïve B cells, switched memory plasmablasts, plasma cells were flow-sorted total IgG anti-U1A (RNP) autoantibodies determined with ELISA.Results: a "memory-like" (CD19 + CD138 -IgM -IgD -) (sMB) phenotype increased...
In vitro studies suggest that the type I interferon (IFN) signature seen in most lupus patients results from Fcγ receptor-mediated uptake of nucleic acid-containing immune complexes by plasmacytoid dendritic cells and engagement endosomal Toll-like receptors. The aim this study was to reexamine pathogenesis IFN vivo.Lupus induced mice injecting pristane. Some were treated with normal immunoglobulin or cobra venom factor deplete complement. evaluated polymerase chain reaction. also determined...
Pristane causes chronic peritoneal inflammation resulting in lupus, which C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of monocytes disease. Impaired bone marrow (BM) egress Ccr2− /− abolished confirming importance recruitment to lung. Circulating Ly6C hi from pristane-treated exhibited increased annexin-V staining comparison...
Tumor necrosis factor α (TNFα) antagonists are effective for treating rheumatoid arthritis and other inflammatory diseases, but their use can be complicated by the development of lupus-like phenomena. This study was undertaken to investigate role TNFα in a murine model lupus.Toll-like receptor 7 (TLR-7) ligand-driven lupus induced injection pristane into C57BL/6 (B6) mice deficient (TNFα(-/-) ) or TNFα-intact B6 as wild-type controls. Autoantibody type I interferon (IFN) production measured...