- Immune Cell Function and Interaction
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Immune responses and vaccinations
- Cancer Immunotherapy and Biomarkers
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Long-Term Effects of COVID-19
- Infection Control and Ventilation
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
La Jolla Institute for Immunology
2020-2023
Fewer SARS-CoV-2–reactive memory CD8 + T cells with “exhaustion” features are present in patients severe versus mild COVID-19.
The impact of genetic variants on cells challenged in biologically relevant contexts has not been fully explored. Here, we activated CD4
Abstract Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies 1–3 . Although studies mouse models solid tumours demonstrated PI3Kδ (PI3Kδi) can induce anti-tumour immunity 4,5 , its effect on humans remains unclear. Here we assessed the effects PI3Kδi AMG319 human patients with head neck cancer neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no....
Mucosal-associated invariant T (MAIT) cells are a subset of lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway mouse human thymus using single-cell RNA sequencing phenotypic metabolic analyses. showed predominant subset, which produced IL-17 (MAIT17), IFN-γ (MAIT1) had not only greatly transcriptomes but also states. MAIT17 exhibited increased lipid uptake, storage, mitochondrial potential...
The contribution of CD4+ T cells to protective or pathogenic immune responses SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis viral antigen-reactive from 32 COVID-19 patients. In patients with severe disease compared mild disease, found increased proportions cytotoxic follicular helper (TFH) and (CD4-CTLs) responding SARS-CoV-2, reduced proportion reactive regulatory cells. Importantly, the CD4-CTLs were highly enriched for expression...
ABSTRACT The contribution of CD4 + T cells to protective or pathogenic immune responses SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis viral antigen-reactive from 32 COVID-19 patients. In patients with severe disease compared mild disease, found increased proportions cytotoxic follicular helper (T FH ) and (CD4-CTLs) responding SARS-CoV-2, reduced proportion reactive regulatory cells. Importantly, the CD4-CTLs were highly enriched for...
Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described cancer immunotherapy target mice, its potential to cause toxicity, specific mode of action with regard cellular targets, and whether can be targeted humans remain unknown. Here, we show that JAML is induced by cell receptor engagement, reveal this induction linked cis-regulatory interactions between the CD3D gene loci. When compared other targets plagued...
ABSTRACT The molecular properties of CD8 + T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes >80,000 virus-reactive from 39 COVID-19 patients and 10 healthy subjects. segregated into two groups based whether dominant cell response was ‘exhausted’ or not. SARS-CoV-2-reactive in exhausted subset were increased frequency displayed lesser cytotoxicity inflammatory features with mild compared severe illness. In contrast,...
Abstract Mucosal-associated invariant T (MAIT) cells are a subpopulation of lymphocytes that respond to microbial metabolites. We performed single-cell RNA sequencing and metabolic analyses MAIT cell subsets in thymus peripheral tissues from mice humans define the heterogeneity developmental pathway these innate-like lymphocytes. show predominant mouse subset, which produces IL-17 (MAIT17), subset IFNγ (MAIT1), have greatly different transcriptomes states periphery. A splenic has...
Abstract Patients with severe uncontrolled asthma represent a distinct endotype persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. To determine T cell subsets effector molecules drive pathogenesis of asthma, we performed single-cell transcriptome analysis >50,000 CD4+ cells isolated from bronchoalveolar lavage (BAL) samples 30 patients mild asthma. We observed striking heterogeneity in the nature present asthmatics' airways tissue-resident...
Abstract Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize vitamin B metabolites. We have performed single-cell RNA (sc-RNA) sequencing of MAIT from thymus, liver, spleen and lung using 10× genomics, where we sequenced more than 7,000 identified 10 clusters by unbiased clustering. the different organs distributed in most clusters; except two were cell specific another consisted exclusively thymus. The cluster reveals a tissue residency gene signature....