A5025364549- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Immunodeficiency and Autoimmune Disorders
- Psoriasis: Treatment and Pathogenesis
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
- Systemic Lupus Erythematosus Research
- Eosinophilic Esophagitis
- Acute Myeloid Leukemia Research
- Whipple's Disease and Interleukins
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Genetic and Kidney Cyst Diseases
- Inflammatory Bowel Disease
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune responses and vaccinations
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- Glycosylation and Glycoproteins Research
- Chronic Myeloid Leukemia Treatments
- Pancreatic and Hepatic Oncology Research
- Cell Adhesion Molecules Research
University of Alabama at Birmingham
2015-2024
Emory University
2000-2007
Emory Healthcare
2001-2002
Suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors the JAK/STAT pathway. SOCS3 has a crucial role in inhibiting STAT3 activation, signaling, and inflammatory gene expression macrophages/microglia. To determine myeloid cells neuroinflammation, mice with conditional deletion (LysMCre-SOCS3 fl/fl ) were tested for experimental autoimmune encephalomyelitis (EAE). The myeloid-specific SOCS3-deficient vulnerable to myelin oligodendrocyte glycoprotein (MOG)-induced EAE,...
Currently there are few reliable cell surface markers that can clearly discriminate effector from memory T cells. To determine if changes in O-glycosylation between these two types, we analyzed virus-specific CD8 cells at various time points after lymphocytic choriomeningitis virus infection of mice. Antigen-specific were identified using major histocompatibility complex class I tetramers, and glycosylation monitored with a monoclonal antibody (1B11) recognizes O-glycans on mucin-type...
ABSTRACT Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of VV-specific T-cell response and how this compares to immune foreign gene(s) expressed by rVV. To address issue, we quantitated responses both viral vector insert following infection mice with VV expressing a cytotoxic T lymphocyte (CTL) epitope (NP118-126) from lymphocytic choriomeningitis virus (LCMV). The LCMV epitope-specific was intracellular...
Abstract Apoptosis is a critical regulator of homeostasis in the immune system. In this study we demonstrate that memory CD8+ T cells are more resistant to apoptosis than naive cells. After whole body irradiation mice, both and decreased number, but reduction number was 8-fold greater addition examining radiation-induced apoptosis, analyzed expansion contraction vivo following exposure Ag. We found not only responded quickly after viral infection, secondary effector generated from underwent...
Abstract Although the role of CD28-B7 interaction in activation naive T cells is well established, its importance generation and maintenance cell memory not understood. In this study, we examined requirement for interactions primary immune memory. Ag-specific CD8 responses were compared between wild-type (+/+) CD28-deficient (CD28−/−) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). During response, there was a substantial expansion LCMV-specific both +/+...
Abstract Pathogenic Th cells and myeloid are involved in the pathogenesis of multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE), an animal model MS. The JAK/STAT pathway is used by numerous cytokines for signaling critical development, regulation, termination immune responses. Dysregulation has pathological implications neuroinflammatory diseases. Many MS/EAE, including IL-6, IL-12, IL-23, IFN-γ, GM-CSF, use to induce biological Thus, targeting JAKs treating inflammation...
Highlights•CD4 T cells rapidly increase mitochondrial respiration during Th17 differentiation•OXPHOS is essential for cell pathogenicity in a mouse model of MS•Mitochondrial shapes the and Treg fate decision•OXPHOS facilitates TCR mTOR signaling, which turn support BATF inductionSummaryUnderstanding metabolic pathways that regulate development important to broaden therapeutic options Th17-mediated autoimmunity. Here, we report pivotal role oxidative phosphorylation (OXPHOS) lineage...
Abstract The developmental pathways of long-lived memory CD8 T cells and the lineage relationship between cell subsets remain controversial. Although some studies indicate two major subsets, central (TCM) effector (TEM), are related lineages, others suggest that these arise maintained independently one another. In this study, we have investigated issue examined differentiation by tracking relationships both endogenous TCR transgenic responses after acute infection. Our data as well...
Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis (MS), debilitating disease the CNS, for which only limited therapeutic interventions are available. Because MS mediated in part by autoreactive T cells, particularly Th17 and Th1 current study, we tested whether inhibitors glycogen synthase kinase-3 (GSK3), previously reported to reduce cell generation, also alter production or alleviate EAE. GSK3 were found impede cells reducing STAT1 activation....
Here, we show that the capacity to manufacture IL-2 identifies constituents of expanded CD8 T cell effector pool display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis by cells attenuates ability receive IL-2-dependent STAT5 signals, thereby limiting terminal formation, endowing IL-2-producing subset with superior protective powers. In contrast, non-IL-2-producing respond signals...
Abstract During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and lectin peanut agglutinin (PNA). We investigated contribution of CD43 expression to PNA as well its role in generation maintenance CD8 cell response. Analysis CD43−/− mice revealed no reduced on virus-specific from −/− compared with +/+ mice. Furthermore, we examined kinetics an immune that modestly effects primary response vivo but plays more significant trafficking tissues...
Abstract CD4+ T cells are critical for host defense but also major drivers of immune-mediated diseases. The classical view Th1 and Th2 subtypes was recently revised by the identification Th17 lineage that produce IL-17, which have been found to be in pathogenesis autoimmune other Mechanisms controlling differentiation well described, few feasible targets therapeutically reducing known. generation requires IL-6 activation STAT3. During polarization cells, we inhibition glycogen synthase...
In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, mice genetically deficient in the transcription factor signal transducer and activator 4 (STAT4) are resistant to disease. contrast, deletion or inhibition Th1-associated cytokines IL-12 IFNγ which act upstream downstream STAT4, respectively, does not ameliorate These discordant findings imply that STAT4 may non-canonical role during EAE. Recently, has been shown regulate GM-CSF production by CD4 T cells...
The role of aberrant glycosylation in pancreatic ductal adenocarcinoma (PDAC) remains an under-investigated area research. In this study, we determined that the ST6GAL1 sialyltransferase, which adds α2,6-linked sialic acids to N-glycosylated proteins, is upregulated patients with early-stage PDAC, and further increased advanced disease. A tumor-promoting function for was elucidated using tumor xenograft experiments human PDAC cells. Additionally, developed a genetically-engineered mouse...
Abstract Excess dietary salt and salt-sensitivity contribute to cardiovascular disease. Distinct T cell phenotypic responses high hypertension as well influences from environmental cues are not understood. The aryl hydrocarbon receptor (AhR) is activated by ligands, promoting systemic homeostasis. We hypothesized that activating AhR supports CD4+ homeostatic functions, such cytokine production mobilization, in response intake while mitigating salt-sensitive hypertension. In the intestinal...