A5089728692- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- Virus-based gene therapy research
- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Cell death mechanisms and regulation
- Osteoarthritis Treatment and Mechanisms
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Polyamine Metabolism and Applications
- interferon and immune responses
- Cytomegalovirus and herpesvirus research
- Autoimmune and Inflammatory Disorders Research
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Galectins and Cancer Biology
- Psoriasis: Treatment and Pathogenesis
- NF-κB Signaling Pathways
University of Alabama at Birmingham
2015-2024
American College of Rheumatology
2018-2024
Birmingham VA Medical Center
2002-2023
National Ilan University
2010-2022
Women's Hospital
2020
Yale University
2017-2020
AID Atlanta
2020
Cathay General Hospital
2019
National Taipei University of Nursing and Health Science
2019
Immunovaccine (Canada)
2007
Abstract Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B responses during progression. Using a syngeneic mouse model lung cancer, we show reduction percentages absolute numbers subsets including pro–, pre–, mature bone marrow (BM) tumor-bearing mice. The kinetics this impaired response correlated with progressive infiltration...
Follicular regulatory T (Tfr) cells act as the counterpart of follicular helper (Tfh) to suppress germinal center (GC) B cell differentiation. We recently showed that interleukin-21 (IL-21) promoted Tfh differentiation in autoimmune BXD2 mice develop spontaneous GCs. This study was undertaken determine modulatory effects IL-21 on Tfr and balance mice.The percentage phenotype were determined BXD2-IL21(-/-) mice. The cell:Tfh ratio evaluated. Sorted from cocultured with cells, or transferred...
We previously identified that autoreactive B cells from BXD2 mice can be targeted by IL-17, leading to upregulation of the expression regulators G-protein signaling (Rgs) genes facilitated development spontaneous germinal centers. Little is known about pathway used IL-17 upregulate RGS. In current study, we found rapidly activates canonical NF-kappaB and exhibit higher basal activated phosphorylated p65 levels than B6 or BXD2-Il17ra(-/-) cells. Inhibition phosphorylation downregulated RGS16...
Germinal centers (GCs) provide a microenvironment that promotes and regulates the interactions of B cells with follicular Th (TFH) cells. In this study, we show there are significantly higher frequencies CXCR5(+)ICOS(+) TFH in autoimmune BXD2 mice, these express both IL-21R IL-17RA. Although IL-17 IL-21 important for formation spontaneous GCs development pathogenic autoantibodies, IL-21, but not IL-17, is required proper mice. The total numbers their ability to induce cell responses vitro...
Objective Fucosylation catalyzed by fucosyltransferases (FUTs) is an important posttranslational modification involved in a variety of biologic processes. This study was undertaken to determine the roles fucosylation rheumatoid arthritis (RA) and assess efficacy reestablishing immune homeostasis with use 2‐deoxy‐ d ‐galactose (2‐ ‐gal), inhibitor. Methods Quantitative polymerase chain reaction performed expression FUT genes synovial tissue from RA osteoarthritis (OA) patients...
The major limitation of adenovirus is its association with induction an inflammatory response and relatively short-term production the gene therapy transgene product. Adeno-associated virus (AAV) a 4.68-kb single-strand DNA that contains ITRs for viral replication packaging signal, also has been engineered to contain therapeutic genes up 5 kb in length. Transduction recombinant AAV (rAAV) results low long-term expression. We have cloned low-immunogenic form human sTNFRI (sTNFRI2.6D) into...
Abstract Beclin 1 is an essential mediator of autophagy and a regulator cell growth death. We examined the effect overexpression on action estradiol (E2) two antiestrogens, raloxifene 4-hydroxytamoxifen, in estrogen receptor α (ERα)-positive MCF-7 breast cancer cells. [3H]-thymidine incorporation studies showed that 1–overexpressing cells (MCF-7.beclin) had lower proliferative response to E2 compared with transfected vector control (MCF-7.control). There was only 35% increase incorporation,...
Abstract Objective To determine the therapeutic efficacy and immunomodulatory effect of an anti‐human death receptor 5 (DR5) antibody, TRA‐8, in eliminating macrophage subsets a mouse model type II collagen–induced arthritis (CIA). Methods A human/mouse‐chimeric DR5‐transgenic mouse, under regulation 3‐kb promoter loxP‐flanked STOP cassette, was generated crossed with ubiquitous Cre (Ubc.Cre) lysozyme M–Cre (LysM.Cre)–transgenic to achieve inducible or macrophage‐specific expression. Chicken...
Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method which could be used to deplete autoreactive T cells in vivo. was toxic, however, and controlled regulation of not achieved. Here describe improved approach delivering TNF-related apoptosis-inducing ligand (TRAIL) vivo collagen II–induced (CII-induced) arthritis–susceptible (CIA-susceptible) DBA/1j mice were treated with CII-pulsed DCs that had been transfected a novel Ad system. The engineered exhibit inducible...
Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method which could be used to deplete autoreactive T cells in vivo. was toxic, however, and controlled regulation of not achieved. Here describe improved approach delivering TNF-related apoptosis-inducing ligand (TRAIL) vivo collagen II–induced (CII-induced) arthritis–susceptible (CIA-susceptible) DBA/1j mice were treated with CII-pulsed DCs that had been transfected a novel Ad system. The engineered exhibit inducible...
Abstract Defective receptor editing or defective B cell checkpoints have been associated with increased frequency of multireactive autoantibodies in autoimmune disease. However, Ig somatic hypermutation and/or class switch recombination may be mechanisms enabling the development pathogenic autoantibodies. In this study, we report that, BXD2 mouse model disease, elevated expression activation-induced cytidine deaminase (AID) recirculating follicular CD86+ subsets cells and germinal center...
The application of AAV2 or AAV8 vectors for delivery human coagulation factor IX (hF.IX) is a promising gene therapy hemophilia B. One major limitation this the development antibodies and cytotoxic T lymphocyte (CTL) response against both vector capsid transgene. We determined class I II MHC peptide epitopes AAV2, AAV8, hF.IX after administration AAV-2-hF.IX AAV8-hF.IX in H2(b) (C57BL/6), H2(d) (BALB/c), H2(k) (C3H) strains mice. results indicate that AA(373-381), AA(50-58), transgene...
The BXD2 strain of mice is one approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres rheumatoid factor (RF) anti-DNA antibody, a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, bone cartilage erosion. features lupus...
Abstract Objective To determine novel genes regulated by tumor necrosis factor α (TNFα) signaling in primary rheumatoid arthritis synovial fibroblasts (RASFs). Methods Oligonucleotide microarrays were used to measure gene expression levels 6 independent replicate samples of RASFs. RASFs transfected for 18 hours with AdIκB–dominant negative (AdIκB‐DN) (n = 3) or control AdTet expressing the reverse tetracycline trans ‐activator 3). The cells stimulated 3 TNFα, and total RNA was prepared....
Abstract Involution of the thymus and alterations in development thymocytes are most prominent features age‐related immune senescence. We have carried out a comparative analysis thymocyte stroma rapid thymic involution DBA/2 (D2) strain mice compared with slow C57BL/6 (B6) mice. Analysis at 15 months age suggested an decrease cell count, block T cells cortical D2 3‐month‐old TUNEL (terminal‐deoxynucleotidyl‐transferase‐mediated dUTP–digoxigenin nick end labelling) staining...