A5017780269- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Eosinophilic Esophagitis
- Reproductive System and Pregnancy
- Hepatitis C virus research
- CAR-T cell therapy research
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- interferon and immune responses
- HIV Research and Treatment
- Dermatology and Skin Diseases
- Nanoplatforms for cancer theranostics
- Cytokine Signaling Pathways and Interactions
- Cancer, Stress, Anesthesia, and Immune Response
- RNA Research and Splicing
- Complement system in diseases
- Inflammasome and immune disorders
- Autoimmune and Inflammatory Disorders Research
- Asthma and respiratory diseases
- RNA modifications and cancer
Cincinnati Children's Hospital Medical Center
2015-2025
University of Cincinnati
2014-2024
University of Cincinnati Medical Center
2016-2024
Children’s Institute
2016-2023
National Student Clearinghouse Research Center
2021-2023
Autoimmune Technologies (United States)
2022
Genomics (United Kingdom)
2022
Division of Undergraduate Education
2021
University of Massachusetts Chan Medical School
2007-2014
University of Virginia
2001-2009
Persistent viral infections are often associated with inefficient T cell responses and sustained high-level expression of inhibitory receptors, such as the NK receptor 2B4 (also known CD244), on virus-specific cells. However, role in dysfunction is undefined, it unknown whether cells contribute to regulation these processes. We show here that persistent lymphocytic choriomeningitis virus (LCMV) infection mice lacking resulted diminished LCMV-specific CD8+ responses, prolonged persistence,...
The goal of most vaccines is the induction long-lived memory T and B cells capable protecting host from infection by cytotoxic mechanisms, cytokines high-affinity antibodies. However, efforts to develop against major human pathogens such as HIV HCV have not been successful, thereby highlighting need for novel approaches circumvent immunoregulatory mechanisms that limit protective immunity. Here, we show mouse natural killer (NK) inhibit generation virus-specific T- well antibody production...
Abstract Dendritic cells (DCs) isolated from patients with chronic hepatitis C virus (HCV) infection display an impaired capacity to generate type 1 CD4+ T cell immunity. Several reports have described immunomodulatory function for the HCV core protein, and circulating has been shown associate putative gC1q receptor, gC1qR, expressed on host immune cells. However, molecular mechanism(s) of core-mediated DC dysfunction not defined. Herein, ligation gC1qR human monocyte-derived DCs (MDDCs) or...
The balance between protective immunity and immunopathology often determines the fate of virus-infected host. How rapidly virus is cleared a function initial viral load, replication rate, efficiency immune response. Here, we demonstrate, with three different inocula lymphocytic choriomeningitis (LCMV), how race T cell responses can result in disease outcomes. A low dose LCMV generated efficient CD8 effector cells, which minimal lung liver pathology. high resulted clonal exhaustion responses,...
The signaling lymphocyte activation molecule (SLAM) family receptor, 2B4/CD244, was first implicated in anti-viral immunity by the discovery that mutations of SLAM-associated protein, SAP/SH2D1A, impaired 2B4-dependent stimulation T and natural killer (NK) cell functions X-linked lymphoproliferative (XLP) syndrome patients with uncontrolled Epstein-Barr virus (EBV) infections. Engagement 2B4 has been variably shown to either activate or inhibit lymphocytes which express this receptor. While...
ABSTRACT Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated 5 (MDA5) are essential intracellular detectors of viral RNA. They contribute to the type interferon (IFN) response that is crucial for host defense against infections. Given potent antiviral proinflammatory activities elicited by IFNs, induction IFN tightly regulated. Members tripartite motif (TRIM) family proteins have recently emerged as key regulators immunity. We show TRIM13, an E3 ubiquitin ligase,...
Highlights•NK cells limit germinal center responses following protein immunization•NK repress antigen-specific B cell and immunoglobulin production•Quantity quality of somatic mutations are inhibited by NK cells•NK suppression affinity maturation is perforin dependentSummarySomatic hypermutation sequences in (GC) reactions must be optimized to elicit high-affinity, protective antibodies after vaccination. We expose natural killer (NK) as robust negative regulators antigen-reactive cells....
Tumor-associated macrophages/microglia (TAMs) are prominent microenvironment components in human glioblastoma (GBM) that potential targets for anti-tumor therapy. However, TAM depletion by CSF1R inhibition showed mixed results clinical trials. We hypothesized GBM subtype-specific tumor (TME) conveys distinct sensitivities to targeting.We generated syngeneic PDGFB- and RAS-driven models resemble proneural-like mesenchymal-like gliomas, determined the effect of targeting inhibitor PLX3397 on...
Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds reduced frequency function natural killer (NK) cell contributes to AD pathogenesis, yet underlying mechanisms contributions NK cells comorbidities remain ill-defined. Here, analysis circulating in longitudinal early life cohort children with revealed progressive accumulation low expression activating receptor NKG2D,...
Complement plays a pivotal role in the regulation of innate and adaptive immunity. It has been shown that binding C1q, natural ligand gC1qR, on T cells inhibits their proliferation. Here, we demonstrate direct hepatitis C virus (HCV) core to gC1qR leads impaired Lck/Akt activation T-cell function. The HCV associates with surface specifically via as this is inhibited by addition either anti-gC1qR antibody or soluble gC1qR. affinity constant protein for determined BIAcore analysis, 3.8 x...
Hepatitis C virus (HCV) is remarkably efficient at establishing persistent infection, suggesting that it has evolved one or more strategies aimed evading the host immune response. T cell responses, including interferon-gamma production, are severely suppressed in chronic HCV patients. The core protein been previously shown to circulate bloodstream of HCV-infected patients and inhibit immunity through an interaction with gC1qR. To determine role core-gC1qR modulation inflammatory cytokine we...
ABSTRACT Persistent viral infections are associated with host and factors that impair effective antiviral immunity. Natural killer (NK) cells contribute to establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection in mice through suppression virus-specific T cell responses during the first few days infection, but NK depletion those early time points can enable severe cell-mediated immune pathology death host. Here we show long after their peak cytolytic activation,...
Thrombin promotes the proliferation and function of CD8+ T cells. To test if thrombin prevents exhaustion sustains antiviral cell activity during chronic viral infection, we depleted thrombin-precursor prothrombin to 10% normal levels in mice prior infection with clone 13 strain lymphocytic choriomeningitis virus. Unexpectedly, insufficiency resulted 100% mortality after that was prevented by depletion cells, suggesting reduced availability enhances virus-induced immunopathology. Yet,...
Abstract gC1qR, a complement receptor for C1q, plays pivotal role in the regulation of inflammatory and antiviral T cell responses. Several pathogens, including hepatitis C virus, exploit gC1qR-dependent regulatory pathways to manipulate host immunity. However, molecular mechanism(s) gC1qR signaling involved regulating responses remains unknown. We report selective inhibition TLR4-induced IL-12 production after cross-linking on surface macrophages dendritic cells. Suppression did not result...
This study tests the hypothesis that activation of MAPK by physiologically relevant concentrations IL-33 contributes to enhanced cytokine expression IL-12 stimulated human NK cells. While canonically triggers type 2 responses, this can also synergize with 1 cytokines like provoke IFN-γ. We show picogram and are sufficient promote robust secretion IFN-γ cells greatly exceeds resposes either alone. Nanogram doses IL-33, potentially consistent levels in tissue microenvironments, induce...