A5046801262- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Extracellular vesicles in disease
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Inflammation biomarkers and pathways
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Immune responses and vaccinations
- Phagocytosis and Immune Regulation
- Neurogenesis and neuroplasticity mechanisms
- interferon and immune responses
- HIV Research and Treatment
- Peripheral Neuropathies and Disorders
- Eosinophilic Esophagitis
- Salivary Gland Tumors Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Pancreatitis Pathology and Treatment
- IL-33, ST2, and ILC Pathways
Columbia University
2024
Columbia University Irving Medical Center
2021-2023
University of Pennsylvania
2017-2023
Centre Hospitalier de l’Université de Montréal
2021
Université de Montréal
2011-2021
Montreal Neurological Institute and Hospital
2014-2019
McGill University
2014-2019
Wayne State University
2019
Hôpital Saint-Luc
2011
GM-CSF–producing B cells contribute to multiple sclerosis pathogenesis and the therapeutic action of cell depletion.
B cells can be enriched within meningeal immune-cell aggregates of multiple sclerosis (MS) patients, adjacent to subpial cortical demyelinating lesions now recognized as important contributors progressive disease. This demyelination is notable for a 'surface-in' gradient neuronal loss and microglial activation, potentially reflecting the effects soluble factors secreted into CSF. We previously demonstrated that MS B-cell products are toxic oligodendrocytes neurons. The potential...
Dimethyl fumarate (DMF), a therapy for relapsing-remitting multiple sclerosis (RRMS), is implicated as acting on inflammatory and antioxidant responses within both systemic immune and/or central nervous system (CNS) compartments. Orally administered DMF rapidly metabolized to monomethyl (MMF). Our aim was analyze the impact of fumarates antiinflammatory profiles human myeloid cells found in compartment (monocytes) inflamed CNS (blood-derived macrophages brain-derived microglia).We analyzed...
Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional relates meningeal subpial injury interest. Using postmortem FFPE...
<h3>Objective:</h3> To document functional differences between monocyte-derived macrophages (MDMs) of patients with MS and the ability age/sex-matched healthy donor cells to phagocytose human myelin investigate molecular mechanisms that underlie this. <h3>Methods:</h3> MDMs were derived from peripheral blood monocytes 25 untreated relapsing-remitting secondary progressive controls (HCs). Phagocytosis was assessed by flow cytometry using fluorescently labeled myelin. Quantification messenger...
The success of clinical trials selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates cells are important contributors to peripheral immune responses involved the development new relapses. Such contribution inflammation likely involves antibody-independent mechanisms. Of growing interest is potential that cells, within MS central nervous system (CNS), may also contribute propagation CNS-compartmentalized progressive (non-relapsing) disease. known persist...
To identify whether factors toxic to oligodendrocytes (OLs), released by B cells from patients with MS, are found in extracellular microvesicles enriched exosomes.
Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the fragile CSF by single-cell RNA sequencing (RNA-seq) in moderate- to large-scale studies. Fresh was collected from twenty-one participants two independent sites. Each sample split into fractions: one processed fresh, while second cryopreserved months and profiled after thawing. B T cell receptor also performed. Our...
Abstract Cerebrospinal fluid (CSF) biomarkers are important for multiple sclerosis (MS) diagnosis. Moreover, absent of autopsy or biopsy tissue, CSF is the most relevant source studying immune cells involved in MS pathophysiology. Single-cell RNA sequencing (scRNA-seq) provides new opportunities to advance our understanding disease-associated changes cells. Here, using scRNA-seq data generated from 58 and 10 PBMC samples, we provide an updated atlas present human other neuroinflammatory...
The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC cell co-cultures, we investigated the effects IL-17A, Th17 hallmark cytokine, on ability to promote de novo infection viral reservoir reactivation. Our results demonstrate that IL-17A acts synergy TNF boost production CCL20, Th17-attractant...
Abstract The polygenic and multi-cellular nature of multiple sclerosis (MS) immunopathology necessitates cell-type-specific molecular studies in order to improve our understanding the diverse mechanisms underlying immune cell dysfunction MS. Here, by generating a dataset 1,075 transcriptomes from 209 participants (167 MS 42 healthy), we assessed MS-associated transcriptional changes six implicated cell-type-states: naïve memory helper T cells classical monocytes purified peripheral blood,...
Immunosenescence (ISC), the aging of immune system, has largely been studied in populations European descent. Here, circulating cell cytometric data from African-American, Hispanic, and non-Hispanic White participants were generated. Known novel age effects identified using either a meta-analysis approach or parallel genetic approach. Most results are consistent across three populations, but some display evidence heterogeneity, such as PD-L1
Abstract B cell depleting therapies efficiently decrease new multiple sclerosis (MS) relapses. Previously, we demonstrated that MS patients harbor abnormally higher proportions of pro-inflammatory effector cells (Beff), producing high IL-6. TNF and GM-CSF levels compared to controls. are fostered within the central nervous system (CNS). Persistence was reported lesions meningeal aggregates, which adjacent subpial cortical injury, involving neuronal loss microglia/macrophage activation, known...
OBJECTIVE: To investigate the effect of IL-10 on phenotypic characteristics M2 polarized human microglia. BACKGROUND: Myeloid cells acquire distinct immunologic phenotypes dependent their state 'polarization': either 'M1' (pro-inflammatory) or 'M2' (anti-inflammatory). cells, generated using mCSF/IL-4/IL13, produce increased quantities anti-inflammatory cytokines and display phagocytic activity expression scavenger receptors. Previous in vitro studies show that mCSF/IL-4/IL13 treated...
Abstract Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional relates meningeal subpial injury interest. Using post-mortem...
OBJECTIVE: To carry out a pilot investigation of the relationship between meningeal inflammation, cortical demyelination and white matter lesional activity in multiple sclerosis (MS) donors with progressive disease. BACKGROUND: Cortical (particularly subpial demyelination) is an important component MS pathology, being associated disease progression cognitive impairment. There have been variable reports on association such inflammation. Some studies reported relative paucity immune cells or...