A5063153847- Immune Cell Function and Interaction
- Viral Infections and Immunology Research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Eosinophilic Disorders and Syndromes
- Nerve injury and regeneration
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Drug-Induced Hepatotoxicity and Protection
- Phytochemical compounds biological activities
- Liver Diseases and Immunity
- CAR-T cell therapy research
- Inflammatory mediators and NSAID effects
- Neuroscience and Neuropharmacology Research
- Axon Guidance and Neuronal Signaling
- Eicosanoids and Hypertension Pharmacology
- Signaling Pathways in Disease
- Alzheimer's disease research and treatments
- Dermatology and Skin Diseases
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Cell Adhesion Molecules Research
Center for Cancer Research
2017-2022
National Cancer Institute
2012-2022
National Institutes of Health
2005-2018
Johns Hopkins University
2005-2015
Johns Hopkins Medicine
2010-2015
The development of opioid-induced analgesic tolerance and hyperalgesia is a clinical challenge for managing chronic pain. Adaptive changes in protein translation the nervous system are thought to promote opioid hyperalgesia; however, how opioids drive such remains elusive. Here, we report that mammalian target rapamycin (mTOR), which governs most translation, was activated rat spinal dorsal horn neurons after repeated intrathecal morphine injections. Activation triggered through μ receptor...
Myocarditis is a leading cause of sudden cardiac failure in young adults. Natural killer (NK) cells, subset the innate lymphoid cell compartment, are protective viral myocarditis. Herein, we demonstrated that these qualities extend to suppressing autoimmune inflammation. Experimental myocarditis (EAM) was initiated BALB/c mice by immunization with myocarditogenic peptide. During EAM, activated NK cells secreted interferon γ, perforin, and granzyme B, expressed CD69, tumor necrosis...
A.SW and B10.S mice share the same major histocompatibility complex (MHC) haplotype (H-2(s)). However, are susceptible to experimental autoimmune myocarditis (EAM) develop severe disease after immunization with myosin, whereas resistant. We found that naive have intrinsically increased total CD4(+) T cell counts proportions of cells in their spleens compared mice. Among cells, a lower relative frequency forkhead box protein 3 (FoxP3(+))CD25(+) regulatory (T(regs)). also had higher proportion...
Abstract The pathogenesis of immune-mediated myocarditis depends on genetic and environmental factors. To study the mechanisms, we have developed a model experimental autoimmune in A.SW mouse. Here provide evidence that loci murine chromosome 6, possibly 1, are involved regulating susceptibility. Moreover, these overlap with implicated other diseases including diabetes NOD These two also regulate apoptosis thymocytes as well peripheral T cells mouse, report further mice demonstrate same...
All T cells are dependent on IL-7 for their development and homeostasis. Foxp3(+) regulatory (Tregs) unique among in that they IL-2. Whether such IL-2 dependency is distinct from or addition to an requirement has been a confounding issue, particularly because of the absence adequate experimental system address this question. In study, we present novel vivo mouse model where expression intact but was geographically limited thymus. Consequently, not available peripheral tissues. Such mice were...
Abstract Neurotrophin‐3 (NT‐3) exerts its trophic effects in brain via tyrosine kinase receptor C (trkC) signaling. TrkC splice variants produce receptors with (full‐length) and without (truncated) a domain. The relative abundance of trkC isoforms the anatomical localization human prefrontal cortex (PFC) relationship to development maturation are currently unknown. We have examined temporo‐spatial expression protein mRNA during PFC. found two major isoforms, full‐length (150 kDa) truncated...
γ-Chain (γc) cytokine receptor signaling is required for the development of all lymphocytes. Why γc plays such an essential role not fully understood, but induction serine/threonine kinase Pim1 considered a major downstream event as prevents apoptosis and increases metabolic activity. Consequently, we asked whether overexpression would suffice to restore lymphocyte in γc-deficient mice. By analyzing Pim1-transgenic mice (Pim1(Tg) γc(KO) ), show that promoted T-cell survival absence γc....
The prosurvival factor Bcl-x L prevents excessive γc cytokine signaling in developing T cells.
Abstract Bone marrow (BM) transplantation has been used to study the cellular basis of genetic control autoimmune diseases, but conclusions remain elusive due contradictory findings in different animal models. In current study, we found that BM cells from myocarditis-susceptible A.SW mice can render irradiated, myocarditis-resistant B10.S recipient susceptible myosin-induced myocarditis, indicating hematopoietic express differences controlling susceptibility myocarditis. We then sought...
Abstract Eosinophilic myocarditis is a likely fatal form of characterized by high mortality, compromised cardiac function, and severe infiltration dominated eosinophils. We have demonstrated that eosinophils are present in the heart contribute to disease severity during murine model experimental autoimmune (EAM). now show natural killer (NK) cells exert control eosinophilic inflammation recruitment. Animals were depleted vivo DX5+CD3- NK i.p. injection anti-asialo GM1 antibody throughout...
Abstract CD103 is a cell surface integrin whose primary role the retention of lymphocytes in epithelial tissues where its ligand E-cadherin expressed. found on all newly generated CD8 single positive thymocytes but not CD4 lineage cells. Because such specific expression, currently considered marker expression proposed to be controlled by Runx3, runt-family transcription factor involved specification. Here we report surprising finding that Runx3 was neither necessary nor sufficient for T...
Abstract Myocarditis is the inflammation of cardiac muscle and among leading causes sudden failure in young adults. We demonstrate here that natural killer (NK) cells, a subset Type I innate lymphoid cell (ILC) group, suppress experimental autoimmune myocarditis (EAM). EAM was initiated BALB/c mice by immunization with myocarditogenic peptide emulsified complete Freund's adjuvant. During disease, activated NK cells accumulated heart, secreted interferonγ, perforin, granzyme-B, expressed...
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Abstract The goal of this study is to identify non-H-2 loci controlling differential susceptibility experimental autoimmune myocarditis (EAM). A.SW and B10.S mice share the same MHC (H-2s) haplotype, yet are susceptible EAM, while resistant. We have identified a locus on Chromosome 1 (termed Eam1) that important in determining myocarditis. In we found naive had higher percentage CD4+ T cells their spleens, from great potential differentiate towards Th17 pathway than mice. To examine why more...
Abstract Autoimmune myocarditis is induced by the adoptive immune response; however, there evidence that innate system plays a major role in modulating disease. Natural killer (NK) cells can function early responses, as well affecting later adaptive response. Depletion of NK has been shown to exacerbate development virus-induced myocarditis. We hypothesized also modulate virus-free model myosin-induced experimental autoimmune (EAM). To study action cells, we immunized BALB/c mice on days 0...