A5010943802- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Oral microbiology and periodontitis research
- Cholesterol and Lipid Metabolism
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Antimicrobial Peptides and Activities
- Angiogenesis and VEGF in Cancer
- Hematopoietic Stem Cell Transplantation
- Salivary Gland Disorders and Functions
- Phagocytosis and Immune Regulation
- Single-cell and spatial transcriptomics
- Axon Guidance and Neuronal Signaling
- Cancer, Lipids, and Metabolism
- Acute Myeloid Leukemia Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hepatitis B Virus Studies
- Virus-based gene therapy research
La Jolla Institute for Immunology
2012-2021
University of Alabama at Birmingham
2005-2012
Czech Academy of Sciences, Institute of Microbiology
2005
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that atherogenesis Treg lose Foxp3 expression and their immunosuppressive function, leading conversion of a fraction these into follicular helper (Tfh) cells. We Tfh are pro-atherogenic depletion reduces atherosclerosis. Mechanistically, correlates with reduced IL-2Rα pSTAT5 levels increased IL-6Rα. In vitro, incubation naive oxLDL prevents differentiation Furthermore, injection...
Throughout the inflammatory response that accompanies atherosclerosis, autoreactive CD4+ T-helper cells accumulate in atherosclerotic plaque. Apolipoprotein B100 (apoB), core protein of low-density lipoprotein, is an autoantigen drives generation pathogenic type 1 (TH1) with proinflammatory cytokine secretion. Clinical data suggest existence apoB-specific T atheroprotective, regulatory cell (Treg) phenotype healthy individuals. Yet, function apoB-reactive Tregs and their relationship TH1...
Abstract In this report we have inspected whether difficulties in controlling viral infections negatively impacts the generation of CD127high memory T cells. Using both MHC class I and II tetramers reveal that CD127low cells are not necessarily rapidly deleted but can persist a pseudoeffector state which they display hallmarks activated effector functionally inferior. can, however, emerge if infection is contained. We also show absence CD4 cell help significant populations CD8 fail to...
ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol accumulation and alters T cell homeostasis, which may contribute to progression of atherosclerosis. Here, we investigated how the selective loss ABCG1 in cells impacts atherosclerosis LDL receptor-deficient (LDLR-deficient) mice, a model disease. In LDLR-deficient mice fed high-cholesterol diet, cell-specific deficiency protected against atherosclerotic lesions. Furthermore, led 30% increase Treg percentages aorta...
Abstract IL-10 produced by T cells and CD11b+ utilizes TLR2 signaling FimA antigen to inhibit early IFN-γ cell responses Porphyromonas gingivalis. P.g., a Gram-negative bacterium, is one of the main etiological agents chronic inflammatory disease, periodontitis. Disease progression thought occur as result an inadequate immune response, which although happens locally, can also distally dissemination P.g. into circulation. As are pivotal molecules in response that elicits, we hypothesized...
Recombinant hemagglutinin B (rHagB), a virulence factor of the periodontal pathogen Porphyromonas gingivalis, has been shown to induce protective immunity against bacterial infection. Furthermore, we have demonstrated that rHagB is TLR4 agonist for dendritic cells. However, it not known how cell stimulation affects activation and differentiation T Therefore, undertook present study examine role signaling in shaping CD4(+) response following immunization mice with rHagB. Immunization this Ag...
Objective: CD4 T cells are important regulators of atherosclerotic progression. The metabolic profile controls their signaling and function, but how atherosclerosis affects T-cell metabolism is unknown. Here, we sought to determine the impact on contribution such alterations atheroprogression. Approach Results: Using PCR arrays, profiled expression genes in from apolipoprotein-E knockout mice fed a Western diet. These exhibited dysregulated critically involved glycolysis fatty acid...
Neuropilin 1 (Nrp1) is a type I transmembrane protein that plays important roles in axonal guidance, neuronal development, and angiogenesis. Nrp1 also helps migrate thymus-derived regulatory T cells to vascular endothelial growth factor (VEGF)-producing tumors. However, little known about the role of on CD4 atherosclerosis. In ApoE-/- mice fed Western diet for 15 wk, we found 2-fold increase Nrp1+Foxp3- their spleens, periaortic lymph nodes, aortas, compared with chow-fed mice. had higher...
In this study we investigate the attributes of virus-specific memory CD8 T cells which most effectively control secondary infections. By rechallenging mice that had cleared primary lymphocytic choriomeningitis virus infections, revealed response is remarkably swift. Within 6 h following infection, production gamma interferon becomes detectable directly ex vivo. During protective phase response, a very early elaboration effector activities preferentially exhibited by specific for viral NP396...
Cardiovascular disease (CVD) remains a significant global health concern with high degree of mortality. While CD4+ T cells have been extensively studied in CVD, the importance CD8+ this disease, despite their abundance and increased activation human atherosclerotic plaques, largely unknown. Thus, objective study was to compare peripheral T-cell signatures between humans (severe) risk CVD (including myocardial infarction or stroke) those low CVD. Approach Results: Using mass cytometry, we...
ABSTRACT A Salmonella vector vaccine expressing the saliva-binding region (SBR) of adhesin AgI/II Streptococcus mutans has been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and require Toll-like receptor 2 (TLR2), TLR4, MyD88 signaling for induction mucosal antibody responses. Since dendritic cells (DC) are critical innate adaptive immunity, present study assessed role SBR expression by DC activation. Bone marrow-derived from wild-type TLR2, knockout were stimulated with...
ABSTRACT Apolipoprotein A1 (ApoA1), the major constituent of high-density lipoprotein (HDL) molecule, exhibits anti-inflammatory properties. Our laboratory has previously shown that ApoA1 protects against switching regulatory T (Treg) cells to atherogenic follicular helper in Western diet-fed mice. However, role modulating Treg cell homeostasis absence atherosclerosis remains uncharacterized. Here, we show is required for normal and functioning at steady state. Specifically, lack decreased...
Apolipoprotein A-I (ApoAI) is the major protein component of HDL. HDL ApoAI involved in efflux cholesterol from cells to maintain cellular homeostasis. also has anti-inflammatory properties. We previously showed that injecting mice fed an atherogenic diet with decreased number activated CD4 lymphocytes. Since T regulatory lymphocytes (Treg) play a role inhibiting immune response during atherosclerosis development, we wanted determine if influences Treg hypothesizing enhances development. To...
Neuropilin 1 (Nrp-1) is a type I transmembrane protein that plays an important role in axonal guidance and neuronal development as well vascular sprouting angiogenesis through the interaction with Semaphorin-3A endothelial growth factor (VEGF), respectively. Recently, Nrp-1 was found on subset of thymus-derived regulatory T cells (Treg) migrated into VEGF producing tumors. Moreover, Nrp-1+ CD4 were protective murine experimental model autoimmune encephalomyelitis, suggesting these may have...
Oxidized phospholipids (OxPL) are ubiquitously generated during inflammation, and found on apoptotic cells, OxLDL, Lp(a). They facilitate uptake of OxLDL by macrophages (Mac) mediate cellular inflammatory responses. The E06 natural IgM binds to the PC OxPL, neutralizing biological effects inhibiting Mac. To determine role OxPL in atherogenesis, we transgenic mice expressing a single chain variant (scFv) Ldlr background (E06-Tg). E06-scFv was secreted into plasma, bound had sufficient titer...
Abstract Background: JULIET, a pivotal phase II trial of Tisa-cel, an anti-CD19 CAR-T cell therapy in pts with r/r LBCL demonstrated durable activity manageable safety profile (Schuster et al., 2021). We sequentially characterized peripheral blood T functionality by immunophenotyping and correlated efficacy endpoints. Methods: Immunophenotypic characterization both non-CAR-T cells was performed flow cytometry 378 samples from 111 collected at enrollment within the first month post Tisa-cel...