A5030230198- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Immunotherapy and Immune Responses
- Food Allergy and Anaphylaxis Research
- Allergic Rhinitis and Sensitization
- IL-33, ST2, and ILC Pathways
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Eosinophilic Esophagitis
- Hereditary Neurological Disorders
- Gut microbiota and health
- Glycosylation and Glycoproteins Research
- Celiac Disease Research and Management
- Asthma and respiratory diseases
- Drug-Induced Adverse Reactions
- Protein Tyrosine Phosphatases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2014-2023
Virginia Mason Medical Center
2022
Benaroya Research Institute
2017-2022
Universitat de Barcelona
2011-2018
Universidad de Salamanca
2005
Abstract Chronic antigenic stimulation can trigger the differentiation of antigen-experienced CD4 + T cells into regulatory type 1 (TR1) cells, a subset interleukin-10-producing Treg that do not express FOXP3. The identities progenitor(s) and transcriptional regulators this T-cell remain unclear. Here, we show peptide-major histocompatibility complex class II (pMHCII) monospecific immunoregulatory pools arise in vivo different genetic backgrounds response to pMHCII-coated nanoparticles...
The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization children and adolescents who were highly allergic to peanut. An improved understanding the immune mechanism induced response food allergen would enable more informed effective therapeutic strategies. Our main purpose was examine immunological changes blood samples from a subset peanut-allergic individuals undergoing AR101.
Systemic delivery of nanoparticles (NPs) coated with mono-specific autoimmune disease-relevant peptide-major histocompatibility complex class II (pMHCII) molecules can resolve organ inflammation in various disease models a disease-specific manner without impairing normal immunity. These compounds invariably trigger the formation and systemic expansion cognate pMHCII-specific T-regulatory type 1 (TR1) cells. By focusing on diabetes (T1D)-relevant pMHCII-NP types that display an epitope from...
Type 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult come by. Here, we devised a combination therapy of peptide/MHC tetramers IL-2/anti-IL-2 monoclonal antibody complexes them over extended time periods. We first optimized treatment protocols conceived obtain improved islet-specific Treg/effector cell ratio that led the vivo expansion activation these as well suppressor function. Optimized...
Abstract Assembly of soluble peptide-major histocompatibility complex class II (pMHCII) monomers into multimeric structures enables the detection antigen-specific CD4 + T cells in biological samples and, some configurations, their reprogramming vivo. Unfortunately, current MHCII-αβ chain heterodimerization strategies are typically associated with low production yields and require use foreign affinity tags for purification, precluding therapeutic applications humans. Here, we show that fusion...
Abstract Autoreactive B cells are essential for the pathogenesis of type 1 diabetes. The genesis and dynamics autoreactive remain unknown. In this study, we analyzed immune response in NOD mouse model to neuronal protein peripherin (PRPH), a target Ag islet-infiltrating cells. PRPH recognized single linear epitope protein, contrast multiple recognition commonly observed during cell responses. Autoantibodies were also detected disease-resistant NOR C57BL/6 strains. To specifically detect...
CD4 T cells are crucial effectors in the pathology of type 1 diabetes (T1D). Successful therapeutic interventions for prevention and cure T1D humans still elusive. Recent research efforts have focused on manipulation by treatment with DNA. In this paper, we studied effects a DNA strategy designed to target antigenic peptides lysosomal compartment monospecific cell population termed 2.5mi(+) that shares reactivity diabetogenic clone BDC-2.5 NOD mouse. MHC class II tetramer analysis showed...
Nanoparticles (NPs) coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHCs) can blunt diseases by re-programming cognate effector T-lymphocytes into disease-suppressing regulatory T-cells, followed massive expansion. Here, a method to quantify the absolute amounts of active drug product is developed, understand relationship between bioavailability and pharmacodynamics. Incubation plasma results in formation protein corona that stabilizes directional pMHC...
The cholera toxin B subunit (CTB) has been used as adjuvant to improve oral vaccine delivery in type 1 diabetes. effect of CTB/peptide formulations on Ag-specific CD4(+) T cells remained largely unexplored. Here, using tetramer analysis, we investigated how CTB fused two T-cell epitopes, the BDC-2.5 2.5 mi mimotope and glutamic acid decarboxylase (GAD) 286-300, affected diabetogenic nonobese diabetic (NOD) mice. When administered i.p., CTB-2.5 activated mi(+) following intragastric generated...
Expression of transcripts for the homotypic adhesion protein epithelial V-like antigen 1 (EVA1), also known as myelin zero like-2 (Mpzl2), is to be present in thymic stromal cells. However, expression within different subsets, and/or lymphoid, has not been characterized due a lack specific reagents. To address this, we generated hybridoma (G9P3-1) secreting monoclonal antibody (G9P3-1Mab), reactive against both human and mouse EVA1. The G9P3-1Mab was by immunizing Mpzl2-deficient...