A5027556015- Immune Cell Function and Interaction
- Reproductive System and Pregnancy
- T-cell and B-cell Immunology
- Pregnancy and preeclampsia studies
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Endometriosis Research and Treatment
- CAR-T cell therapy research
- Pregnancy and Medication Impact
- Ovarian cancer diagnosis and treatment
- Reproductive Biology and Fertility
- Immune Response and Inflammation
- Ovarian function and disorders
- Prenatal Screening and Diagnostics
- Maternal and fetal healthcare
- Reproductive tract infections research
- Migraine and Headache Studies
- NF-κB Signaling Pathways
- Neuroscience of respiration and sleep
- Neonatal and fetal brain pathology
- Lipid Membrane Structure and Behavior
- Endometrial and Cervical Cancer Treatments
- Glycosylation and Glycoproteins Research
- Neonatal Respiratory Health Research
- Nicotinic Acetylcholine Receptors Study
University of Wisconsin–Madison
2016-2024
University of Bern
2024
Hudson Institute
2022-2023
UnityPoint Health Meriter
2023
Meriter Hospital
2023
Waldorf College
2021-2022
Landwirtschaftlichen Zentrums Baden-Württemberg
2022
UW Health University Hospital
2020
Vanderbilt University
2001-2018
Harvard University
2013-2014
Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell–mediated autoimmunity. Vα14 natural killer (NKT) cells are subset of lymphocytes that recognize glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I–like protein CD1d. Here, we show activation NKT glycosphingolipid α-galactosylceramide (α-GalCer) protects susceptible mice against EAE. β-GalCer, which binds CD1d but is not recognized cells, failed to protect...
CD1d-restricted natural killer T (NKT) cells are a subset of regulatory that react with glycolipid antigens. Although preclinical studies have effectively targeted NKT for immunotherapy, little is known regarding the early in vivo response these to antigenic stimulation. We analyzed antigens and bacterial infection by using specific reagents tracking cells. Our results demonstrate dramatic expansion surface phenotype alterations after cell activation α-galactosylceramide. In addition, we...
Human natural killer (NK) T cells are unique lymphocytes that express an invariant cell receptor (TCR) Vα24-Vβ11 and have been implicated to play a role in various diseases. A subset of NKT CD4 hence potential targets for human immunodeficiency virus (HIV)-1 infection. We demonstrate both resting activated Vα24+ high levels the HIV-1 coreceptors CCR5 Bonzo (CXCR6), but low CCR7, as compared with conventional cells. Remarkably α-galactosylceramide (α-GalCer)-pulsed dendritic were profoundly...
Abstract Semi-invariant NKT cells are thymus-derived innate-like lymphocytes that modulate microbial and tumor immunity as well autoimmune diseases. These immunoregulatory properties of acquired during their development. Much has been learned regarding the molecular cellular cues promote cell development, yet how these maintained in thymus periphery they acquire functional competence incompletely understood. We found IL-15 induced several Bcl-2 family survival factors thymic splenic vitro....
Abstract Va14Ja18 natural T (iNKT) cells are innate, immunoregulatory lymphocytes that recognize CD1d-restricted lipid Ags such as α-galactosylceramide (αGalCer). The functions of iNKT dependent upon either IFN-γ or IL-4 production by these cells. We hypothesized αGalCer presentation different CD1d-positive cell types elicits distinct functions. In this study we report dendritic (DC) play a critical role in αGalCer-mediated activation and subsequent transactivation NK Remarkably, B suppress...
Va14Ja18 natural T (NKT) cells play an immunoregulatory role, which is controlled by a self glycolipid(s) presented CD1d. Although the synthetic antigen α-D-galactosylceramide (α-D-GalCer) stimulates all NKT cells, α-anomeric D-glycosylceramides are currently unknown in mammals. We have used β-D-GalCer-deficient mice and β-D-glucosylceramide (β-D-GlcCer)-deficient to define chemical nature of cell antigen. exhibit normal development function, from these animals potently stimulate hybridomas....
Natural killer T (NKT) cells are a unique immunoregulatory cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown NKT exhibit autoreactivity, which raises the question of whether they subject to negative selection. Here, we report addition agonist glycolipid α-galactosylceramide (α-GalCer) fetal thymic organ culture (FTOC) induces dose-dependent disappearance cells, suggesting susceptible Overexpression CD1d in transgenic (Tg) mice results...
Abstract CD1d1 is a member of family lipid Ag-presenting molecules. The cellular ligands associated with were isolated and characterized by biochemical means as an approach to elucidate the mechanism which CD1 molecules assemble in vivo. Natural mouse included phosphatidylinositol phosphatidylinositol-glycans that are synthesized endoplasmic reticulum. Further data revealed two mutants, one defective recycling from-and-to plasma membrane other efficiently negotiating secretory pathway,...
T lineage commitment occurs in a discrete, stage-specific manner during thymic ontogeny. Intrathymic precursor transfer experiments and the identification of CD4(+)8+ double-positive (DP), V alpha 14J 18 natural (iNKT) cells suggest that to this might occur at DP stage. Nevertheless, matter remains contentious because others failed detect 18-positive iNKT are CD4(+)8+. In resolution issue, we demonstrate retinoic acid receptor-related orphan receptor gamma (ROR gamma)0/0 thymi, which...
Atherosclerosis is a disease marked by lipid accumulation and inflammation. Recently, atherosclerosis has gained recognition as an autoimmune-type syndrome characterized increased activation of the innate acquired immune systems. Natural killer T (NKT) cells have characteristics both conventional NK recognize glycolipid antigens presented in association with CD1d molecules on antigen-presenting cells. The capacity NKT to respond modulate immunity suggests that they may play role...
Abstract Ontogenetic, homeostatic, and functional deficiencies within immunoregulatory natural T (iNKT) lymphocytes underlie various inflammatory immune disorders including autoimmunity. Signaling events that control cell fate specification molecular differentiation of iNKT cells are only partly understood. Here we demonstrate these processes require classical NF-κB signaling. Inhibition signaling blocks ontogeny at an immature stage reveals apparent, novel precursor in which negative...
Abstract Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that accompanied by the emergence of autoreactive T cells and reduction in regulatory cells. Humans mice with SLE have reduced numbers CD1d-restricted NK cells, suggesting role for these regulation SLE. In this study, we show CD1d deficiency exacerbates nephritis induced hydrocarbon oil pristane. This exacerbation associated with: 1) TNF-α IL-4 production especially during induction phase; 2) expansion marginal zone...
Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of receptor beta-chain repertoire and how alpha-galactosylceramide (alpha-GalCer) analogues induce responses have remained elusive. Using altered ligands, we discovered that Vb impacts recognition Ag avidity, stimulation suboptimal avidity results in preferential...
Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. The underlying mechanisms are poorly understood, and investigations been hampered by the absence of animal models that reflect human condition generalized atherosclerosis lupus. We addressed this problem transferring susceptibility to low-density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice, an established model atherosclerosis, creating radiation chimeras NZM2410-derived, lupus-susceptible, B6.Sle1.2.3...
Abstract The rapid and robust immunoregulatory cytokine response of Va14Ja18 natural T (iNKT) cells to glycolipid Ags determines their diverse functions. Unlike conventional cells, iNKT lymphocyte ontogeny absolutely requires NF-κB signaling. However, the precise role in cell function identity upstream signals that activate this subset remain unknown. Using mice which has been rescued despite inhibition signaling, we demonstrate a lymphocyte-intrinsic manner. Furthermore, functional...
The CD1 family consists of lipid antigen-presenting molecules, which include group I CD1a, CD1b, and CD1c II CD1d proteins. Topologically, they resemble the classical peptide MHC molecules except that large, exclusively nonpolar hydrophobic, antigen-binding groove has evolved to present cellular pathogen-derived antigens specific T lymphocytes. As an approach understanding biochemical basis antigen presentation by we have characterized natural ligands associated with mouse CD1d1 as well...
Problem The anti‐inflammatory impact of three polyunsaturated fatty acids (3‐ PUFA ) in endometriosis is incompletely understood. effect 3‐ on endometriosis‐like lesions evaluated as a potential treatment target. Method Study Wild Type ( WT and transgenic Fat‐1 mice (high levels endogenous were utilized uterine tissue transplant model. Experimental donor × host pairs included: WW ), WF FF ). Cytokine content IL ‐1β, ‐2, ‐4, ‐6, ‐10, ‐12, ‐17A, IFN ‐γ, TNF MCP ‐1 RANTES immunocellular...
NBSGW mice are highly immunodeficient and carry a hypomorphic mutation in the c-kit gene, providing host environment that supports robust human hematopoietic expansion without pre-conditioning. These thus provide model to investigate engraftment absence of conditioning-associated damage. We compared transplantation CD34+ HSPCs purified from three different sources: umbilical cord blood, adult bone marrow G-CSF mobilized peripheral blood. blood were significantly more efficient (as function...