A5011126910- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Multiple Sclerosis Research Studies
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Parasites and Host Interactions
- Diabetes and associated disorders
- Retinal Diseases and Treatments
- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Ocular Diseases and Behçet’s Syndrome
- Oral microbiology and periodontitis research
- Immunodeficiency and Autoimmune Disorders
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Asthma and respiratory diseases
- interferon and immune responses
- Polyomavirus and related diseases
- Reproductive System and Pregnancy
- Cytomegalovirus and herpesvirus research
- Mast cells and histamine
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory Biomarkers in Disease Prognosis
University of Michigan
2014-2023
Scleroderma Foundation
2021
Center for Rheumatology
1992-2020
Autoimmune Technologies (United States)
2020
Michigan United
2013-2019
W.K. Kellogg Foundation
2017
Michigan Medicine
2017
The University of Texas at Austin
2010
Wuhan University
2008
A. Alfred Taubman Health Care Center
2005
Abstract Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that Food and Drug Administration approved for treatment relapsing-remitting multiple sclerosis. To better understand therapeutic effects Tecfidera its rare side effect progressive multifocal leukoencephalopathy, we conducted cross-sectional longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived untreated 4–6 18–26 mo Tecfidera-treated...
Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of central nervous system (CNS). Due to progressive neurodegenerative nature MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) an oral formulation fumaric acid esters (FAE), containing active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates clinical trials, its mechanism action MS not yet well...
Abstract Introduction Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and assessment patients with established rheumatoid arthritis (RA). However, the PD development remains unclear. This investigation was undertaken to determine contribution chronic immune activation joint inflammation using collagen-induced (CIA) model. Methods DBA1/J mice orally infected Porphyromonas gingivalis were administered collagen II (CII) emulsified in...
Events that occur in rheumatoid arthritis synovial tissues are responsible for the signs and symptoms of joint inflammation eventual destruction articular periarticular structures lead to dysfunction disability. The three most abundant cell populations RA synovium macrophages (type A synoviocytes), fibroblasts B synoviocytes) infiltrating T lymphocytes. Other important include lymphocytes, dendritic cells, plasma mast cells osteoclasts. Our current understanding is moving beyond previous...
Abstract Objective To assess the ability of rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) to function as antigen‐presenting cells (APCs) for arthritogenic autoantigens found within inflamed joint tissues. Methods Human class II major histocompatibility complex (MHC)–typed FLS were used APCs murine MHC–restricted CD4 T cell hybridomas. Interferon‐γ (IFNγ)–treated, antigen‐loaded cocultured with hybridomas specific immunodominant portions human cartilage gp‐39 (HC gp‐39) or type...
ABSTRACT Bruton’s tyrosine kinase (Btk) is a signaling molecule that plays important roles in B-1 B cell development and innate myeloid functions has recently been identified as target for therapy of lymphomas. We examined the contribution cells to resistance Cryptococcus neoformans infection by utilizing X-linked immunodeficient (XID) mice (CBA-CaHN-XID), which possess mutation Btk. XID had significantly higher brain fungal burdens than controls 6 weeks after with C. strain 52D (CN52D);...
We have previously reported that adoptive transfer of tumor-draining lymph node (TDLN) B cells confers tumor regression in a spontaneous pulmonary metastasis mouse model breast cancer. In this study, we identified IL-10-producing within these cells, and found IL-10 removal, either by using IL-10(-/-) TDLN or systemic neutralization IL-10, significantly augmented the therapeutic efficacy adoptively transferred cells. Depletion B-cell transfers increased CTLs activity PBMCs splenic recipient....
Immune suppression mediated by exosomes is an emerging concept with potentially immense utility for immunotherapy in a variety of inflammatory contexts, including allogeneic transplantation. Exosomes containing the apoptosis-inducing molecule Fas ligand (FasL) have demonstrated efficacy inhibiting antigen-specific immune responses upon adoptive transfer animal models. We report here that very high frequency human B cell-derived lymphoblastoid cell lines (LCL) constitutively produce...
To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS).Peripheral blood B cells were compared for surface marker expression RRMS prior to initiation of treatment, after 4-6 months, and at more than 1 year treatment BG-12. Production interleukin (IL)-10 by patient was also analyzed.Total numbers peripheral lymphocytes declined months BG-12 due losses both CD27+ memory CD27(neg) subsets. Some...
Protein kinase C (PKC) isoenzymes are essential components of cell signaling. In this study, we investigated the regulation PKC-alpha in murine B16 amelanotic melanoma (B16a) cells by monohydroxy fatty acids 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and 13(S)-hydroxyoctadecadienoic [13(S)-HODE]. 12(S)-HETE induced a translocation to plasma membrane focal adhesion plaques, leading enhanced B16a matrix protein fibronectin. However, 13(S)-HODE inhibited these effects on PKC-alpha. A...
ABSTRACT A previous study of the murine model Schistosoma mansoni infection has implicated splenic CD19 + B lymphocytes as Fas ligand (FasL)-bearing mediators CD4 T-lymphocyte apoptosis. The present shows that B-cell deficiency leads to decreased T-cell apoptosis during and compares FasL expression killer function B-1a- CD5 − B-lymphocyte subsets. B-1a cells from uninfected mice displayed constitutive compared with cells. was enhanced following worm egg deposition antigenic stimulation on...
ABSTRACT Granuloma formation around schistosomal eggs is induced by soluble egg antigens (SEA) and mediated the activity of CD4 + Th lymphocytes their cytokines. Regulation inflammatory cell response during infection still insufficiently understood. The hypothesis this study was that activation-induced death (AICD) T cells involved in immune response. This investigated dynamics splenic granuloma apoptosis Fas ligand (FasL) expression acute chronic stages murine infection. Enhanced freshly...
The objective was to study immune regulation in a mouse model of rheumatoid arthritis that exhibits considerable heterogeneity disease activity.T-cell receptor transgenic mice, which nearly all CD4+ T cells recognize single peptide type II collagen, were immunized with collagen and observed for development 4 weeks. At 28 days post-immunization, splenocytes analyzed by flow cytometry vitro assays markers activation regulation.Disease severities ranging from 0 12 (on 12-point scale) observed....
Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we begun to understand complexities of this inter-relationship. As our sophistication about inner workings every aspect immune system has increased, also become obvious schistosome infections broad ranging effects on nearly all innate and adaptive response mechanisms. Selective pressures both their hosts, no doubt led co-evolution protective mechanisms, particularly those favor granuloma...
BACKGROUNDSiponimod (BAF312) is a selective sphingosine-1-phosphate receptor 1 and 5 (S1PR1, S1PR5) modulator recently approved for active secondary progressive multiple sclerosis (SPMS). The immunomodulatory effects of siponimod in SPMS have not been previously described.METHODSWe conducted multicentered, randomized, double-blind, placebo-controlled AMS04 mechanistic study with 36 participants enrolled the EXPAND trial. Gene expression profiles were analyzed using RNA derived from whole...
A hallmark of regulatory B cells is IL-10 production, hence their designation as IL-10+ cells. Little known about the ability self-antigens to induce in Graves' disease (GD), Hashimoto's thyroiditis (HT), or other autoimmune disease. Here we pulsed purified from 12 HT patients, GD and healthy donors with thyroid self-antigen, thyroglobulin (TG) added back remaining peripheral blood mononuclear (PBMCs). This procedure induced B-cell differentiation GD. similar tendency was observed donors,...
Induction of immune tolerance is a key process by which the system educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding harnessing natural mechanisms may become an increasingly useful strategy for treating many types allergic autoimmune diseases, well improving acceptance solid organ transplants. Our laboratory others have been interested in ability some B lymphocytes express death-inducing molecule Fas ligand (FasL), their kill T...