Biology subjects

Magill, I.

Publications and source records attributed to Magill, I..

7 recordsLinked to original sources

bioRxiv2026

immgenT Treg: A Reference Landscape of Regulatory T Cell States in Mice

CD4+FoxP3+ regulatory T cells (Tregs) are central to immunity, tolerance, and tissue homeostasis, yet their extensive heterogeneity lacks a unifying framework. Within the immgenT project, we profiled gene expression, surface markers and TCR clonotypes of mouse Tregs. Using a joint RNA-protein deep generative model, we define the Treg landscape, organized around eight conserved clusters shared across tissues and conditions, with immune context reshaping their relative abundance rather than generating new states, including a prominent circulating effector Treg population enriched in select non-lymphoid tissues. We validate this framework by integrating external datasets from conditions not represented in immgenT and by defining a flow cytometry panel spanning the Treg landscape. Together, immgenT provides a scalable, reusable reference that unifies Treg heterogeneity across tissues and immune challenges.

immunology↗

bioRxiv2026

immgenT: A Comprehensive Reference of Convergent T-cell States in the Mouse

The immgenT collaborative project generated a comprehensive molecular atlas of T cells spanning virtually all mouse organs and disease states, profiling ~800,000 cells from 750 samples with RNA, 128-plex surface protein, and {beta}TCR sequence. Applying a deep generative model to joint RNA and protein data defined the landscape of T-cell states organized into eight lineages and 107 robust clusters, integrating similar cells from different contexts, and resolving prior nomenclatures. Analysis of effector molecules, transcription factors and modules showed that both immunological functions and regulatory programs are shared across cell states. This framework provides a stable, reusable reference, demonstrated by computationally integrating 16 external datasets from diverse biological contexts. A set of public web tools supports browsing of these data and mapping of any dataset onto the immgenT framework. These results propose a molecular classification of T cells organized around a set of shared states reused across immunological contexts.

immunology↗

bioRxiv2026

The αβTCR repertoire at scale in the immgenT dataset

The immense T cell receptor (TCR) repertoire is shaped by VDJ combinatorial diversity, imprecise rearrangements, and clonal selection. The immgenT Project generated scRNA and TCRseq to map paired {beta}TCR repertoires across 734 mouse samples from diverse tissues and challenge conditions. Compositional analysis uncovered some extreme junctional architectures. Beyond probabilistic V and J pairing, over-represented joins suggested non-randomness in fine joining, broadening the precedent of quasi-invariant iNKT and MAIT TCRs. We charted public clonotypes linked to self or environmental antigens in the main lineages. Tissue analyses revealed compartmentalized tissue-specific expansions. Unproductive and productive rearrangements of a V gene appeared to interfere specifically with each other, at chromatin or RNA levels. Unexpectedly, allelic exclusion at TCR{beta} proved less stringent than thought, and we identified rearrangements of TCR in immature pre-T stages. This organism-wide look into the TCR repertoire offers novel insights on the evolutionary and immunological pressures on TCR repertoire selection.

immunology↗

bioRxiv2025

Epidermal Resident Memory T Cell Fitness Requires Antigen Encounter in the Skin

CD8+ tissue resident memory T cells (TRM) develop from effectors that seed peripheral tissues where they persist providing defense against subsequent challenges. TRM persistence requires autocrine TGF{beta} transactivated by integrins expressed on keratinocytes. TRM precursors that encounter antigen in the epidermis during development outcompete bystander TRM for TGF{beta} resulting in enhanced persistence. ScRNA-seq analysis of epidermal TRM revealed that local antigen experience in the skin resulted in an enhanced differentiation signature in comparison with bystanders. Upon recall, TRM displayed greater proliferation dictated by affinity of antigen experienced during epidermal development. Finally, local antigen experienced TRM differentially expressed TGF{beta}RIII, which increases avidity of the TGF{beta}RI/II receptor complex for TGF{beta}. Selective ablation of Tgfbr3 reduced local antigen experienced TRM capacity to persist, rendering them phenotypically like bystander TRM. Thus, antigen driven TCR signaling in the epidermis during TRM differentiation results in a lower TGF{beta} requirement for persistence and increased proliferative capacity that together enhance epidermal TRM fitness.

immunology↗

bioRxiv2024

Genomic Specificity of Anti-TCR mAbs determined by single-cell RNAseq

T cells play a pivotal role in the immune system, relying on their somatically rearranged T cell receptor (TCR) to recognize peptide-MHC complexes. A comprehensive and extensively used set of monoclonal antibodies (mAbs) against TCR Variable regions was generated in the previous century. The separate identification of mAb-specific TCR-V proteins and TRV genes has resulted in multiple nomenclatures, making their relationships unclear. To formally re-establish this link and determine patterns of reactivity within TRV subfamilies, we sorted T cells positive for any one of a panel of 22 anti-V mAbs and determined their TRV genes by single-cell TCRseq. RNAseq data revealed consistently higher expression of repeated elements from the ERV1-family LTR RLTR6Mm (mapping to Gm20400) in cells utilizing TRBV segments encoded within a 66kb genomic region between TRBV23 and TRBV30. Our findings provide a comprehensive resource for anti-TCR mAb specificity and insight into V-gene usage biases and T cell function.

immunology↗

bioRxiv2024

Expansion of mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis

Pregnancy brings about profound changes in the mammary gland to prepare for lactation, yet immunocyte changes that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells, revealing a marked increase in CD4+ and CD8+ T effector cells, including an expansion of TCR{beta}+CD8+ cells, in pregnancy and lactation. T cells were localized in the mammary epithelium, resembling intraepithelial lymphocytes (IELs) typically found in mucosal tissues. Similarity to mucosal tissues was substantiated by demonstrating partial dependence on microbial cues, T cell migration from the intestine to the mammary gland in late pregnancy, and shared TCR clonotypes between intestinal and mammary tissues, including intriguing public TCR families. Putative counterparts of mammary IELs were found in human breast and milk. Mammary T cells are thus poised to manage the transition from a non-mucosal tissue to a mucosal barrier during lactogenesis.

immunology↗

bioRxiv2023

PD-1 Mediated Regulation of Unique Activated CD8+ T Cells by NK Cells in the Submandibular Gland

The increasing utilization of anti-PD-1 immune checkpoint blockade (ICB) has led to the emergence of immune-related adverse events (irAEs), including sicca syndrome. Interestingly, we found that the submandibular gland (SMG) of PD-1 deficient mice harbors a large population of CD8+ T cells, reminiscing ICB induced sicca. This phenotype was also observed in the SMG of both NK cell-depleted C57BL/6 animals and NK cell-deficient animals. Mechanistically, using mice conditionally deficient for PD-L1 in the NK cell lineage, we discovered that NK cells regulate CD8+ T cell homeostasis via the PD-1/PD-L1 axis in this organ. Importantly, single-cell RNA sequencing of PD-1 deficient SMG CD8+ T cells reveals a unique transcriptional profile consistent with TCR activation. These cells have limited TCR diversity and phenotypically overlap with GzmK+ CD8+ T autoimmune cells identified in primary Sjogrens syndrome patients. These insights into NK cell immunoregulation in the SMG, and the consequences of disrupted CD8+ T cell homeostasis, provide opportunities for preventing the development of irAEs. HighlightsO_LIElevated CD8+ T cells in the submandibular gland (SMG) of PD-1 deficient mice parallel sicca-like irAEs seen in ICB patients. C_LIO_LIIn addition to their previously described hyporesponsive phenotype, NK cells in the SMG regulate CD8+ T cell homeostasis through the PD-L1/PD-1 axis. C_LIO_LIPD-1 deficient SMG CD8+ T cells display unique transcriptional profiles associated with proinflammatory functions, TCR activation, interferon stimulation, and exhaustion. C_LIO_LIOligoclonal expansion and similarities in TCR sequences indicate T cell activation and a preference for recognizing specific antigens. C_LI

immunology↗