A5075811485- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Pancreatic function and diabetes
- Systemic Lupus Erythematosus Research
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Diabetes Management and Research
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Biochemical and Molecular Research
- Protein purification and stability
- Diet, Metabolism, and Disease
- Viral Infections and Vectors
- Vector-borne infectious diseases
- Epigenetics and DNA Methylation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mosquito-borne diseases and control
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Cancer Immunotherapy and Biomarkers
Yale University
2011-2023
University of Florida
2019
New York Medical College
2014
University of California, Irvine
2014
Central Research Institute of Epidemiology
2014
Nantucket Cottage Hospital
2014
Mansfield University
2014
Izhevsk State Medical Academy
2014
University of New Haven
2012
Center for Rheumatology
1999-2006
Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603–607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, 2003. Immunity. 19:837–847) established the unique capacity of DNA DNA-associated autoantigens to activate autoreactive B cells via sequential engagement cell antigen receptor (BCR) Toll-like (TLR) 9. We demonstrate that this two-receptor paradigm can be extended BCR/TLR7 activation by RNA...
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany grafts GVHD by attacking recipient tissues; therefore, all patients receive prophylaxis depletion from the allograft or through immunosuppressant drugs. In addition to providing graft-versus-leukemia effect, donor are critical for reconstituting cell–mediated immunity. Ideally, immunity infectious agents would be transferred host...
A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present mouse autoreactive in immunogenic form. This could account role foreign antigens not only but also tolerance, leading sustained production absence antigen.
Antibodies against U small nuclear ribonucleoprotein (snRNP) particles are a common finding in the sera of humans with SLE and certain strains mice murine lupus. It is likely that Th cells important amplifying this autoantibody response. The focus work was to investigate events might initiate autoimmune B T cell response non-autoimmune native snRNP particles. Mice were immunized boosted mouse snRNPs failed produce any detectable specific anti-snRNP antibody or responses, suggesting these...
The Lyme disease spirochete, Borrelia burgdorferi, causes persistent mammalian infection despite the development of vigorous immune responses against pathogen. To examine spirochetal phenotypes that dominate in hostile environment, mRNA transcripts four prototypic surface lipoproteins, decorin-binding protein A (DbpA), outer C (OspC), BBF01, and VlsE, were analyzed by quantitative reverse transcription-PCR under various conditions. We demonstrate B. burgdorferi changes its antigenic...
The normal functioning immune system is programmed to attack foreign pathogens and other proteins while maintaining tolerance self-proteins. mechanisms by which broken in the initiation of autoimmunity are not completely understood. In present study, mice immunized with murine cytochrome c peptide 90–104 showed no response B or T cell compartments. However, immunization isoaspartyl form this peptide, where linkage Asp93 Leu94 occurs through β-carboxyl group, resulted strong autoimmune...
Abstract West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, thereby partially mimicking human disease. Using this model, we have demonstrated that mice deficient γδ T cells are more susceptible to WN infection. TCRδ−/− elevated viral loads and greater dissemination of the pathogen CNS. In wild-type expanded significantly during infection, produced IFN-γ ex vivo assays, enhanced perforin expression by splenic cells. Adoptive transfer reduced susceptibility these virus,...
Abstract The initiation of autoimmune B cell and T responses by self Ag or foreign pathogens (molecular mimics) is not well understood. In the present study, cytochrome c (cyt c) was used as a model autoantigen to investigate how self-proteins are involved in priming responses. Immunization with cyt has been extensively analyzed previous studies for both humoral cellular immune Mice do not, however, make antibody immunization (mouse) c. addition, tolerance can be broken autoreactive cells...
Abstract Borrelia miyamotoi sensu lato, a relapsing fever sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in all disease–endemic areas of United States. To determine seroprevalence IgG against lato northeastern States assess whether serum from lato–infected persons reactive to antigens, we tested archived samples area residents during 1991–2012. Of 639 healthy persons, 25 were positive for 60 burgdorferi. Samples ≈10%...
The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring type 1 diabetes (T1D)-associated autoantibodies and concordance results among laboratories. IASP organizes international interlaboratory assay comparison studies in which blinded serum samples are distributed participating laboratories, followed by centralized collection analysis results, providing participants with an unbiased comparative assessment. In this report, we describe...
Target tissues of four autoimmune diseases show similar gene expression signatures emphasizing a dialog immune cell-target tissue.
It is now clear that antigen presenting cells (APCs) do not present all the possible peptides of self-proteins to immune system. When then, fate T specific for those self-peptides escape processing? In this study, COOH-terminal peptide (residues 81-104) self cytochrome c (cyt c) elicited strong autoimmune cells, as well autoantibodies immunogen. These did respond stimulation with whole cyt molecule, demonstrating APCs cannot process and 81-104 peptide. Whereas mice were unresponsive...
While respiratory failure in cystic fibrosis (CF) frequently associates with chronic infection by Pseudomonas aeruginosa, no single factor predicts the extent of lung damage CF. To elucidate other causes, we studied autoantibody profile CF and rheumatoid arthritis (RA) patients, given similar association airway inflammation autoimmunity RA. Even though observed that bactericidal permeability-increasing protein (BPI), carbamylated proteins, citrullinated proteins all localized to neutrophil...
The β-cell has become recognized as a central player in the pathogenesis of type 1 diabetes with generation neoantigens potential triggers for breaking immune tolerance. We report that posttranslationally modified glucose-regulated protein 78 (GRP78) is novel autoantigen human diabetes. When islets were exposed to inflammatory stress induced by interleukin-1β, tumor necrosis factor-α, and interferon-γ, arginine residue R510 within GRP78 was converted into citrulline, evidenced liquid...
Objective High‐expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to the severity systemic lupus erythematosus (SLE). The U1 small nuclear RNP (snRNP) immune complex containing snRNP and anti–U1 antibodies, which found in patients with SLE, activates NLRP3 inflammasome, comprising NLRP3, ASC, procaspase 1, human monocytes, leading production interleukin‐1β (IL‐1β). This study was undertaken investigate role up‐regulating expression MIF its interface...
Checkpoint inhibitors (CPIs) targeting programmed death 1 (PD-1)/programmed ligand (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have revolutionized cancer treatment but can trigger autoimmune complications, including CPI-induced diabetes mellitus (CPI-DM), which occurs preferentially with PD-1 blockade. We found evidence of pancreatic inflammation in patients CPI-DM shrinkage pancreases, increased enzymes, a case from patient who died CPI-DM, peri-islet lymphocytic infiltration. In...
Abstract Systemic lupus erythematosus is characterized by high titers of autoantibodies directed at multiple proteins the U1/Sm small nuclear ribonucleoproteins (snRNPs). The origin this type autoimmunity, that is, whether it initiated foreign molecular mimics or self-snRNPs, not known. In study using normal mice, we investigated presence autoreactive B and T cells to D protein murine snRNPs. Although neither nor cell responses could be detected after immunization with native two synthetic...
The U1 small nuclear ribonucleoprotein (sn-RNP) particle, which consists of the RNA and multiple polypeptides, is a central target autoimmune response in systemic lupus erythematosus. Autoantibodies to individual proteins snRNP typically co-occur patients with erythematosus, an observation reconciled by postulating that intact RNA-protein complex serves as autoimmunogen snRNP-specific autoreactive T cells are necessary for autoantibody production. In this study, we demonstrated normal mice...
Abstract Both B cells and dendritic (DCs) have been implicated as autoantigen-presenting in the activation of self-reactive T cells. However, most self-proteins are ubiquitously and/or developmentally expressed, making it difficult to determine source exposure autoantigens APCs a controlled manner. In this study, we used an Ig transgenic mouse model examine mechanisms by which other acquire present lupus vivo. Targeting autoantigen, small nuclear ribonucleoprotein particle D protein, BCR...