A5081452290- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Dermatology and Skin Diseases
- Phagocytosis and Immune Regulation
- Cytomegalovirus and herpesvirus research
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- vaccines and immunoinformatics approaches
- Gut microbiota and health
- Exercise and Physiological Responses
- Inflammatory Bowel Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- SARS-CoV-2 and COVID-19 Research
- Tryptophan and brain disorders
- Inflammatory mediators and NSAID effects
- Lymphoma Diagnosis and Treatment
Broad Institute
2021-2025
Massachusetts Institute of Technology
2021-2024
Massachusetts General Hospital
2023
Harvard University
2021-2023
University of California, Berkeley
2010-2019
Child Trends
2017
Inserm
2009-2013
Institut Pasteur
2009-2013
Fondation de l'Avenir
2009-2010
Asthma is a chronic disease most commonly associated with allergy and type 2 inflammation. However, the mechanisms that link airway inflammation to structural changes define asthma are incompletely understood. Using human model of allergen-induced exacerbation, we compared lower mucosa in allergic asthmatics non-asthmatic controls using single-cell RNA sequencing. In response allergen, asthmatic epithelium was highly dynamic up-regulated genes involved matrix degradation, mucus metaplasia,...
Abstract Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from esophageal mucosa of 7 healthy 15 EoE participants, revealing 60 subsets functional alterations in states, compositions, that highlight previously unclear features EoE. Active displays enrichment ALOX15 + macrophages, PRDM16 dendritic expressing...
Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate depletion is not fully understood. In particular, the anatomical location, type effector cells, mechanism underlying remain uncertain. Here, we found that liver major site recirculation accounts decrease numbers observed secondary lymphoid organs. Using intravital imaging, established that, upon treatment, Kupffer cells (KCs)...
Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic diseases are thought to be driven by both the nervous and immune systems, but fundamental molecular cellular interactions that trigger development of acute-to-chronic transition remain unknown. Here, we show skin-infiltrating neutrophils key initiators in atopic dermatitis, most disorder. Neutrophil depletion significantly attenuated itch-evoked scratching mouse model dermatitis. Neutrophils were...
Autophagy is an essential cellular process that deeply integrated with innate immune signaling; however, studies examine the impact of autophagic modulation in context inflammatory conditions are lacking. Here, using mice a constitutively active variant autophagy gene Beclin1, we show increased dampens cytokine production during model macrophage activation syndrome and adherent-invasive Escherichia coli (AIEC) infection. Moreover, loss functional through conditional deletion Beclin1 myeloid...
Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in induction of peripheral regulatory T (Tregs) immune tolerance to microbiota self-antigens. These APCs encompass Janus Thetis cell subsets, some express AutoImmune REgulator (AIRE). + MHCII type 3 innate lymphoid (ILC3) also been instruction...
Plasma cells (PCs) constitute a significant fraction of colonic mucosal and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA antibodies, their role UC pathogenesis is unknown. We performed single-cell V(D)J- RNA-seq on sorted B from the colon healthy individuals patients with UC. A large cell clones shared between different regions, but inflammation broadly disrupts this landscape, causing transcriptomic changes characterized by...
Abstract Monoclonal antibodies represent a promising approach to fight variety of tumors, but their mode action remains be fully understood. NK cells can recognize Ab-coated targets, as well stress ligands, on tumor cells. In this study, we investigated how integrate both kinds activating signals. cell–mediated killing was maximal with the combined recognition NKG2D ligands and Ab; surprisingly, only engagement substantially enhanced degranulation. Conversely, Ab by uniquely increased...
Enteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is considerably lacking. Here, we characterized a primary sensory (PSN) subset producing the neuromedin U (NMU) and calcitonin gene-related peptide β (CGRPβ) coexpressing receptors for type 2 cytokines interleukin-4 (IL-4) IL-13. Type amplified NMU CGRPβ expression in PSNs, vitro vivo, which was abrogated...
Abstract The liver is a vital organ composed of parenchymal, nonparenchymal, and immune cell populations, which are now being mapped at single resolution. Here we present detailed map the cellular composition human through single-nucleus RNA sequencing (snRNA-seq), incorporating insights from 32 healthy samples. dataset contains cells female male donors spanning more than seven decades age. Excluding X Y chromosome, identified ∼500 genes uniquely enriched in liver, ∼600 liver. These tend to...
NK cells are cytotoxic lymphocytes that most efficient at fulfilling their functions after a phase of priming provided by cytokines and/or accessory cells. Although type I IFNs known to be important in this process, it remains unclear whether they act directly on or indirectly We used adoptive transfer experiments and mixed bone marrow chimeras dissect the requirement for IFN signaling response dsRNA analog polyinosinic-polycytidylic acid. demonstrate optimal cell requires signal both In...
Abstract Neutrophils are generally the first immune cells recruited during development of sterile or microbial inflammation. As these express many innate receptors with potential to directly recognize endogenous signals, we set out assess whether their functions locally influenced by signals present at onset Using a mouse model peritonitis, demonstrate that neutrophils elicited in presence C-type lectin receptor ligands have an increased ability produce cytokines, chemokines, and lipid...
Abstract Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but spatial organization at single-cell resolution not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map zonal distribution hepatocytes, resolve subsets macrophage mesenchymal populations, investigate relationship between hepatocyte ploidy gene expression healthy liver. We next integrated...