A5073464643- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Autoimmune and Inflammatory Disorders Research
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous lymphoproliferative disorders research
- Immune Response and Inflammation
- Systemic Sclerosis and Related Diseases
- Cancer Immunotherapy and Biomarkers
- Inflammasome and immune disorders
- Adolescent and Pediatric Healthcare
- Dermatology and Skin Diseases
- Glycosylation and Glycoproteins Research
- Kawasaki Disease and Coronary Complications
- Poxvirus research and outbreaks
- Platelet Disorders and Treatments
- Herpesvirus Infections and Treatments
- Eosinophilic Disorders and Syndromes
- Inflammatory Myopathies and Dermatomyositis
- Acute Lymphoblastic Leukemia research
- Dermatological and Skeletal Disorders
- Systemic Lupus Erythematosus Research
- Congenital Diaphragmatic Hernia Studies
University of Colorado Denver
2017-2024
Duke University
2024
University of Colorado Anschutz Medical Campus
2021-2023
Children's Hospital Colorado
2018-2023
Penn State Milton S. Hershey Medical Center
2022
RELX Group (United States)
2021
Harvard University
2009-2020
Boston Children's Hospital
2002-2020
Brigham and Women's Hospital
2010-2019
Boston University
2008-2015
Chemotactic factors are postulated to direct emigration of lymphocytes from the blood stream into sites inflammation. Members a family chemotactic cytokines, termed chemokines, have been shown attract but efficacy, i.e., maximal percentage attracted cells, has low. We identified highly efficacious lymphocyte activity in supernatants murine bone marrow stroma cell line MS-5 which attracts 10-fold more vitro than currently described chemoattractants. Purification this revealed identity stromal...
Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.
E-selectin plays a critical role in mediating tissue-specific homing of T cells into skin, and primitive hematopoietic progenitor (HPCs) bone marrow (BM). Though it is known that glycoform PSGL-1 (CLA) functions as the principal ligand on human lymphocytes, ligand(s) HPCs has not been identified. We used shear-based adherence assay to analyze define activity membrane proteins from HPCs. Our data show expressed an ligand, also express previously unrecognized CD44. The CD44 conferred by...
Abstract CD4+CD25+ T regulatory cells (Treg) are thought to be important in the peripheral tolerance. Recent evidence suggests that human blood heterogeneous and contain both CD4+CD25high with potent activity many more CD4+CD25low/med nonregulatory cells. In this study, we found virtually all CD4+CD25highFoxp3+ Treg expressed high levels of chemokine receptor CCR4. addition, 80% cutaneous lymphocyte Ag (CLA) 73% CCR6. These molecules were functional, as CLA+ showed CD62E ligand demonstrable...
We demonstrate an additional step and a positive feedback loop in leukocyte accumulation on inflamed endothelium. Leukocytes shear flow bind to adherent leukocytes through L-selectin/ligand interactions subsequently downstream roll endothelium, purified E-selectin, P-selectin, L-selectin, VCAM-1, or peripheral node addressin. Thus nucleate formation of strings rolling cells synergistically enhance accumulation. Neutrophils, monocytes, activated T cell lines, but not blood lymphocytes, tether...
Abstract Objective Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although wide range of therapeutic strategies has been reported in the literature, lack agreement on treatment specifics accepted methods for clinical assessment made it difficult to compare approaches identify optimal therapy. Our objective was develop standardized plans, assessments, response criteria active, moderate high severity juvenile...
Studies of interleukin 1 (IL-1) alpha and beta have emphasized their functional similarities. IL-1 -beta are encoded by ancestrally related genes that diverged dramatically in primary sequence; however, only modest differences the regulation or biological activity been documented. Here we show mouse L cells transfected with murine pro-IL-1 cDNA expressed biologically active, 33-kilodalton alpha, this pro molecule was neither processed to 17-kilodalton mature form nor secreted. The also...
Murine peritoneal exudate cells (PEC), analyzed immediately after isolation, did not express detectable IL 1 activity or 1-specific mRNA. Stimulation of these by adherence induced the expression intracellular, membrane, and extracellular activities within 4 hr. Analysis mRNA from showed a concurrent induction both alpha beta However, this stimulation was transient, since PEC cultured for 5 days no longer expressed bioactivity specific quiescent with bacterial lipopolysaccharide re-expression...
Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD lesions. We show that application antigen mouse subjected tape stripping, surrogate for scratching, induces an IL-22 response drives hyperplasia proliferation model inflammation shares many features AD. DC-derived IL-23 act on CD4+ T production. However, the...
Rheumatoid arthritis is a systemic autoimmune disease, but disease flares typically affect only subset of joints, distributed in distinctive pattern for each patient. Pursuing this intriguing pattern, we show that recurrence mediated by long-lived synovial resident memory T cells (TRM). In three murine models, CD8+ bearing TRM markers remain previously inflamed joints during remission. These are bona fide TRM, exhibiting failure to migrate between preferential uptake fatty acids, and...
The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite extravasation into tissues. Our results indicate that DCs express both HECA-452-reactive and nonreactive isoforms P-selectin glycoprotein ligand 1 (PSGL-1) can tether roll efficiently on E- under flow conditions vitro. Freshly isolated were further observed continuously along noninflamed murine dermal endothelium vivo. This interaction is strictly...
Selectin interactions with glycolipids have been examined previously under static conditions, whereas physiologic mediated by selectins take place flow. We find that flow sialyl Lewis(x) (sLe(x)) glycolipid and Lewisa (sLe(a)) neoglycolipid support tethering rolling adhesions of Chinese hamster ovary (CHO) cells expressing E-selectin lymphoid myeloid L-selectin. These selectin-mediated persist at the highest shear stresses occur in postcapillary venules vivo lower site densities than found...
Abstract Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence definitive diagnostic markers limits the accuracy clinical evaluations suspected KD with significant increases in morbidity. In turn, incomplete understanding its molecular pathogenesis hinders identification rational targets needed to improve therapy. We used high‐accuracy mass spectrometry proteomics analyse over 2000 unique proteins urine specimens patients KD. discovered that proteomes KD, but not those...