A5084845268- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- HIV Research and Treatment
- Single-cell and spatial transcriptomics
- Health, Environment, Cognitive Aging
- Epigenetics and DNA Methylation
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Immunotherapy and Immune Responses
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Optimism, Hope, and Well-being
- Psoriasis: Treatment and Pathogenesis
- Childhood Cancer Survivors' Quality of Life
- Neuroinflammation and Neurodegeneration Mechanisms
- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- Circadian rhythm and melatonin
- Spaceflight effects on biology
- Reproductive System and Pregnancy
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Nutrition, Genetics, and Disease
- Microscopic Colitis
- Immunotoxicology and immune responses
Scripps Research Institute
2011-2025
The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
2023-2024
Biomedical Research Institute
2022
University of Florida
2022
The thymus is the most rapidly aging tissue in body, with progressive atrophy beginning as early birth and not later than adolescence. Latent regenerative potential exists atrophic thymus, because certain stimuli can induce quantitative regrowth, but qualitative function of T lymphocytes produced by regenerated organ has been fully assessed. Using a genome-wide computational approach, we show that accelerated thymic primarily stromal cells, while overall cellularity be restored, many other...
T lymphocytes are essential mediators of immunity that produced by the thymus in proportion to its size. The atrophies rapidly with age, resulting progressive diminution new cell production. This decreased output is compensated duplication existing cells, but it results gradual dominance memory cells and ability respond pathogens or vaccines. Here, we show accelerated irreversible thymic atrophy from stromal deficiency reducing enzyme catalase, leading increased damage hydrogen peroxide...
Highlights•Expression of Aire and self-antigen genes decreases with age in thymic B cells•B cell-intrinsic cell-extrinsic mechanisms contribute to this decline expression•The phenotype transcriptome cells change age•T-bet expression frequency IgG2a increase aged cellsSummaryAlthough autoimmune disorders are a significant source morbidity mortality older individuals, the governing age-associated increases susceptibility remain incompletely understood. Central T cell tolerance is mediated...
Abstract T lymphocytes must be produced throughout life, yet the thymus, where are made, exhibits accelerated atrophy with age. Even in advanced atrophy, however, thymus remains plastic, and can regenerated by appropriate stimuli. Logically, thymic is thought to reflect senescent cell death, while regeneration requires proliferation of stem or progenitor cells, although evidence scarce. Here we use conditional reporters show that reflects contraction complex projections unique cortical...
Inflammatory bowel disease (IBD) involves chronic T cell-mediated inflammatory responses. Vedolizumab (VDZ), a monoclonal antibody against α4β7 integrin, inhibits lymphocyte extravasation into intestinal mucosae and is effective in ulcerative colitis (UC) Crohn's (CD).
Thymic atrophy reduces naive T cell production and contributes to increased susceptibility viral infection with age. Expression of tissue-restricted antigen (TRA) genes also declines age has been thought increase autoimmune disease susceptibility. We find that diminished expression a model TRA gene in aged thymic stromal cells correlates impaired clonal deletion cognate recognizing an autoantigen involved atherosclerosis. Clonal the polyclonal thymocyte population is perturbed. Distinct...
Ongoing viral transcription from the reservoir of HIV-1 infected long-lived memory CD4 + T cells presents a barrier to cure and associates with poorer health outcomes for people living HIV, including chronic immune activation inflammation. We previously reported that didehydro-cortistatin A (dCA), an Tat inhibitor, blocks transcription. Here, we examine impact dCA on host T-cell transcriptional epigenetic states. performed comprehensive analysis genome-wide transcriptomic DNA methylation...
Despite numerous therapeutic options, safe and curative therapy is unavailable for most patients with chronic lymphocytic leukemia (CLL). A drawback of current therapies such as the anti-CD20 monoclonal antibody (mAb) rituximab elimination all healthy B cells, resulting in impaired humoral immunity. We previously reported identification a patient-derived, CLL-binding mAb, JML-1, identified sialic acid-binding immunoglobulin-like lectin-6 (Siglec-6) target JML-1. Although little known about...
Abstract The zinc-finger transcription factor GATA-3 plays a crucial role during early T cell development and also dictates later differentiation outcomes. However, its collaboration with the Notch signaling pathway in induction of lineage specification commitment have not been fully elucidated. We show that deficiency mouse hematopoietic progenitors results an block despite presence signals, failure to upregulate Bcl11b expression, leading diversion along myeloid, but B cell, fate....
Abstract T lymphocytes develop in the thymus, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells (TSCs) directs along a well-characterized differentiation program. However, biology of comprising lymphopoietic microenvironment remains relatively under-characterized because are rare difficult to isolate. Using deconvolution technique study gene expression essentially situ, we previously identified deficiency peroxide quenching enzyme catalase (CAT) cells,...
Abstract Individual naive CD8 T cells activated in lymphoid organs differentiate into functionally diverse and anatomically distributed cell phylogenies response to intracellular microbes. During infections that resolve rapidly, including live viral vaccines 1 , distinct effector (T EFF ) memory MEM populations develop ensure long term immunity 2 . chronic infections, responding progressively become dysfunctional “exhaust” 3 A taxonomy of exhausted EX is known, but the initial developmental...
Abstract T lymphocytes are essential mediators of immunity produced by the thymus in proportion to mass. The atrophies rapidly with age, resulting diminished new cell production. Decreased thymic output is compensated duplication existing cells, but results progressive dominance memory and decreased ability respond pathogens or vaccines. We find that accelerated atrophy from stromal deficiency reducing enzyme catalase, leading increased damage reactive oxygen species (ROS) generated during...
Abstract Disclosure: J.C. Nwachukwu: None. J.W. Njeri: T. Venables: C. Seath: M.E. Pipkin: Y. Hou: B.S. Katzenellenbogen: J.A. K.W. Nettles: We recently developed Dual Mechanism Estrogen Receptor-α (ERα) Inhibitors (DMERI) with more antagonist efficacy than selective ERα modulators (SERMs) such as tamoxifen, and degraders (SERDs) fulvestrant in certain breast cancer models. Current models of anti-estrogen action are largely based on genomics studies growth arrested cells, where the effects...
CD8
Abstract T lymphocytes develop in the thymus, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells (TSCs) directs along a well-characterized differentiation program. However, biology of comprising lymphopoietic microenvironment remains relatively under-characterized because are rare difficult to isolate. Using deconvolution technique study gene expression essentially situ, we previously identified deficiency peroxide quenching enzyme catalase (CAT) cells,...
Abstract Age-associated thymic atrophy results in diminished production of new T lymphocytes and a concomitant decrease responsiveness to pathogens vaccines. In addition loss size with age, critical stromal functions, including tissue-restricted antigen (TRA) expression, are age. We previously identified deficiency the hydrogen peroxide quenching enzyme catalase (CAT) cells as cause during aging, established that can be mitigated by genetic or dietary complementation antioxidant activity....
Abstract The primary site for the development of T lymphocytes is thymus, where cross-talk between thymic stromal cells (TSCs) and cell progenitors mediates maintenance both populations. However, thymus begins to atrophy relatively early in life, resulting diminished output, corresponding immunodeficiencies aged individuals. Our previous studies revealed that express conspicuously low levels peroxide quenching enzyme catalase (CAT), which results high reactive oxygen species (ROS)...
Abstract T lymphocytes develop in the thymus, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells directs along a well-characterized program of differentiation. However, biology comprising lymphopoietic microenvironment remains relatively under-characterized because are rare difficult to isolate. Using deconvolution technique study gene expression essentially situ, we previously identified deficiency peroxide quenching enzyme catalase (CAT) cells, found...
Abstract T lymphocytes develop in the thymus, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells (TSCs) directs along a well-characterized program of differentiation. However, biology TSCs comprising lymphopoietic microenvironment remains relatively under-characterized because are rare difficult to isolate. Using deconvolution technique study gene expression essentially situ, we previously identified deficiency H202 quenching enzyme catalase (CAT) TSCs,...