A5001698827- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Immune responses and vaccinations
- Systemic Lupus Erythematosus Research
- Chronic Lymphocytic Leukemia Research
- Single-cell and spatial transcriptomics
- Blood disorders and treatments
- Immunotherapy and Immune Responses
- Blood groups and transfusion
- Acute Myeloid Leukemia Research
- Vaccine Coverage and Hesitancy
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- Cell Adhesion Molecules Research
- Neuroscience of respiration and sleep
- HIV Research and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Platelet Disorders and Treatments
- Cancer-related molecular mechanisms research
- T-cell and Retrovirus Studies
- Chemokine receptors and signaling
- Cellular Mechanics and Interactions
Inserm
2023-2025
Université de Toulouse
2023-2025
Centre National de la Recherche Scientifique
2013-2025
Children's Hospital of Philadelphia
2017-2024
University of Pennsylvania
2018-2022
Philadelphia University
2022
Institut de Biologie Moléculaire et Cellulaire
2013
Immunologie, Immunopathologie et Chimie Thérapeutique
2013
Hôpital de la Timone
2005
Follicular helper T cells (TFH) represent a distinct subset of CD4+ specialized in providing help to B lymphocytes, which may play central role autoimmune diseases having major cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with from germinal centers, have been described the peripheral blood healthy individuals. The aim this study was analyze distribution populations patients. Circulating were defined by...
Abstract Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of variant accessibility gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear characteristic SLE. Of ~400 potential regulatory identified, 90% exhibit proximity...
Abstract Inhibition of Bruton’s Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little known; however, about how BTKi influences MS disease-implicated functions B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, attenuates B-cell:T-cell interactions via novel mechanism involving modulation metabolic pathways which, turn, mediates an...
The mechanisms by which FOXP3+ T follicular regulatory (Tfr) cells simultaneously steer antibody formation toward microbe or vaccine recognition and away from self-reactivity remain incompletely understood. To explore underappreciated heterogeneity in human Tfr cell development, function, localization, we used paired TCRVA/TCRVB sequencing to distinguish tonsillar that are clonally related natural (nTfr) those likely induced helper (Tfh) (iTfr). proteins iTfr nTfr differentially expressed...
The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. deficiency fatally arrests lymphopoiesis myelopoiesis in mice, but human congenital disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients...
Abstract Background SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. disease severity has been associated with some pre-existing conditions the magnitude adaptive immune response SARS-CoV-2, recent genome-wide association study (GWAS) risk critical illness revealed significant genetic component. To gain insight into how human variation attenuates exacerbates following infection, we implicated putatively functional...
Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, kidneys being one main target organs. As source pathogenic antibodies, plasma cells therefore critical players in this harmful scenario, both at and local levels. The aim present study was analyze NZB/W mice get a better understanding mechanisms underlying their involvement renal inflammation process. Using...
B cells within secondary lymphoid tissues encompass a diversity of activation states and multiple maturation processes that reflect antigen recognition transition through the germinal center (GC) reaction, in which mature differentiate into memory antibody-secreting (ASCs). Here, utilizing single-cell RNA-seq, we identify range distinct tonsil-derived cells. In particular, what believe is previously uncharacterized CCL4/CCL3 chemokine-expressing cell population with an expression pattern...
T follicular regulatory (T fr ) cells can counteract the B cell helper activity of fh and hinder production antibodies against self-antigens or allergens. A mechanistic understanding cytokines initiating differentiation human reg into is still missing. Herein, we report that low doses pro-T cytokine interleukin-12 (IL-12) drive induction a program on activated while also preserving their function. Mechanistically, found IL-12 led to STAT4 (signal transducer activator transcription 4)...
SUMMARY Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy immunocompromised individuals has not yet been performed due to challenge directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled immune nodes kidney transplant (KTX) recipients. We found...
Located contiguously on the long arm of second chromosome are gene paralogs encoding immunoglobulin-family co-activation receptors CD28 and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). CTLA4 share same B7 ligands yet each provides opposing proliferative signals to T cells. Herein, we describe for first time two unrelated subjects with coexisting haploinsufficiency due heterozygous microdeletions 2q. Although their clinical phenotype, multi-organ inflammatory disease, is superficially...
Clearance of HIV-infected germinal center (GC) CD4+ follicular helper T cells (Tfh) after combination antiretroviral therapy (ART) is essential to an HIV cure. Blocking B cell lymphoma 6 (BCL6; the master transcription factor for Tfh cells) represses infection tonsillar ex vivo, reduces GC formation, and limits immune activation in vivo We assessed anti-HIV activity a novel BCL6 inhibitor, FX1, Tfh/non-Tfh its impact on SAMHD1 phosphorylation (Thr592). FX1 repressed HIV-1 peripheral (P <...
ABSTRACT Systemic lupus erythematosus (SLE) is a complex inflammatory disease mediated by autoreactive antibodies that damages multiple tissues in children and adults. Genome-wide association studies (GWAS) have statistically implicated hundreds of loci the susceptibility to human disease, including SLE, but majority failed identify causal variants or effector genes. As physicochemical approach detecting functional connecting them target genes, we generated comprehensive, high-resolution...
Abstract How FOXP3 + T follicular regulatory (Tfr) cells simultaneously steer antibody formation toward microbe/vaccine recognition and away from self-reactivity remains unsettled. To explore human Tfr cell provenance, function location heterogeneity, we used paired TCRVA / TCRVB sequencing to distinguish tonsillar clonally related natural Tregs (nTfr) those likely induced Tfh (iTfr). The proteins iTfr nTfr differentially expressed were utilized pinpoint their in situ locations via...