Work

Systems mapping of intra-donor, cross-tissue T cell clonal expansion and tissue adaptation in the gut-liver-blood axis

Year: 2026

Type: article

Abstract: The human gut-liver axis is a critical immunological interface, yet factors that shape T cell adaptation and clonal expansion across tissues remain unclear. We performed integrated single-cell RNA and T cell receptor sequencing on T cells from matched colon epithelium, lamina propria, liver, and blood of the same donors, enabling clonal tracking and tissue-specific transcriptional profiling without inter-individual confounders. Colonic intraepithelial lymphocytes were largely clonally distinct from lamina propria T cells. Tissue-resident T cells in colon vs. liver displayed marked transcriptional divergence, with colonic lamina propria tissue-resident memory T cells (TRMs) enriched for interferon-stimulated genes (e.g., ISG15 and IFITM3). Ligand-receptor analysis implicated liver-derived factors, including fibrinogen gamma chain, in shaping colon TRM states. Across tissues, highly expanded clones of the same cell type shared a core upregulated gene set, suggesting common determinants of clonal success. These data provide a same-donor single-cell atlas of T cell diversity and adaptation across the human gut-liver-blood axis.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.116916

Authors: Ran Ran, Merve Uslu, Mohd Farhan Siddiqui, Douglas K. Brubaker, Martin Trapecar

Institutions: Case Western Reserve University, Johns Hopkins University, Johns Hopkins All Children's Hospital, University Hospitals of Cleveland

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620