Biology subjects

Jarvis, L. B.

Publications and source records attributed to Jarvis, L. B..

5 recordsLinked to original sources

bioRxiv2024

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

The immune system comprises multiple cell lineages and heterogeneous subsets found in blood and tissues throughout the body. While human immune responses differ between sites and over age, the underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach to comprehensively profile RNA and surface protein expression of over 1.25 million immune cells isolated from blood, lymphoid organs, and mucosal tissues of 24 organ donors aged 20-75 years. We applied a multimodal classifier to annotate the major immune cell lineages (T cells, B cells, innate lymphoid cells, and myeloid cells) and their corresponding subsets across the body, leveraging probabilistic modeling to define bases for immune variations across donors, tissue, and age. We identified dominant tissue-specific effects on immune cell composition and function across lineages for lymphoid sites, intestines, and blood-rich tissues. Age-associated effects were intrinsic to both lineage and site as manifested by macrophages in mucosal sites, B cells in lymphoid organs, and T and NK cells in blood-rich sites. Our results reveal tissue-specific signatures of immune homeostasis throughout the body and across different ages. This information provides a basis for defining the transcriptional underpinnings of immune variation and potential associations with disease-associated immune pathologies across the human lifespan.

immunology↗

bioRxiv2023

Hiding in Plain Sight: Thymic CD8+FOXP3+Tregs sequester CD25 and are enriched in human tissues

For decades, regulatory T cell (Treg) research has focussed on CD4+FOXP3+ Tregs, while characterisation of CD8+FOXP3+ Tregs has been limited due to their scarcity in blood. Here, by analysing 95 tissue samples from 26 deceased transplant organ donors we show that, despite representing less than 5% of circulating Tregs, CD8+ Tregs are enriched in human tissue, particularly in non-lymphoid tissues and bone marrow. We further show that they are fully demethylated at the FOXP3 TSDR, indicating lineage stability, and demonstrate their presence in human thymic tissue and cord blood. Transcriptomic profiling revealed strong similarities to CD4+ Tregs, however at the protein level, they reside in tissue as surface CD25lo/-CD8+CD69+CD103+TLR9+HELIOS+FOXP3+ cells, expressing CD25 intracellularly. Surface CD25 was rapidly regained ex-vivo, allowing us to sort and expand them, and to subsequently demonstrate their therapeutic potential in a humanised mouse model of graft-vs-host disease. Additionally we report increased circulating CD8+Tregs in individuals with SLE and patients early following traumatic brain injury (TBI), underscoring their functional importance. We conclude that these under-studied cells likely play an essential but previously unappreciated role in maintaining peripheral tolerance. One Sentence SummaryFOXP3+CD8+ Tregs, expressing tissue residency markers and intracellular CD25, are enriched in human non-lymphoid tissues.

immunology↗

bioRxiv2023

FlowAtlas.jl: an interactive tool bridging FlowJo with computational tools in Julia

As the dimensionality, throughput, and complexity of cytometry data increases, so does the demand for user-friendly, interactive analysis tools that leverage high-performance machine learning frameworks. Here we introduce FlowAtlas.jl: an interactive web application that bridges the user-friendly environment of FlowJo and computational tools in Julia developed by the scientific machine learning community. We demonstrate the capabilities of FlowAtlas using a novel human multi-tissue, multi-donor immune cell dataset, highlighting key immunological findings.

bioinformatics↗

bioRxiv2021

Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture across the human body

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing. One Sentence SummaryWe provide an immune cell atlas, including antigen receptor repertoire profiling, across lymphoid and non-lymphoid human tissues.

immunology↗

bioRxiv2019

Distinct microbial and immune niches of the human colon

Gastrointestinal microbiota and immune cells interact closely and display regional specificity, but little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterisation of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady-state. We describe distinct T helper cell activation and migration profiles along the colon and characterise the transcriptional adaptation trajectory of T regulatory cells between lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal expansion and mutational frequency from caecum to sigmoid colon, and link this to the increasing number of reactive bacterial species.

immunology↗