Ran Ran, Uslu Merve, Siddiqui Mohd Farhan, Brubaker Douglas K, Trapecar Martin
Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH.
Department of Medicine, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
bioRxiv. 2025 Mar 14:2025.03.11.642626. doi: 10.1101/2025.03.11.642626.
Understanding T cell clonal relationships and tissue-specific adaptations is crucial for deciphering human immune responses, particularly within the gut-liver axis. We performed paired single-cell RNA and T cell receptor sequencing on matched colon (epithelium, lamina propria), liver, and blood T cells from the same human donors. This approach tracked clones across sites and assessed microenvironmental impacts on T cell phenotype. While some clones were shared between blood and tissues, colonic intraepithelial lymphocytes (IELs) exhibited limited overlap with lamina propria T cells, suggesting a largely resident population. Furthermore, tissue-resident memory T cells (TRM) in the colon and liver displayed distinct transcriptional profiles. Notably, our analysis suggested that factors enriched in the liver microenvironment may influence the phenotype of colon lamina propria TRM. This integrated single-cell analysis maps T cell clonal distribution and adaptation across the gut-liver-blood axis, highlighting a potential liver role in shaping colonic immunity.
了解T细胞克隆关系和组织特异性适应性对于解读人类免疫反应至关重要，尤其是在肠-肝轴内。我们对来自同一人类供体的匹配结肠（上皮、固有层）、肝脏和血液中的T细胞进行了配对单细胞RNA和T细胞受体测序。这种方法追踪了不同部位的克隆，并评估了微环境对T细胞表型的影响。虽然血液和组织之间存在一些共享克隆，但结肠上皮内淋巴细胞（IEL）与固有层T细胞的重叠有限，表明其主要是常驻群体。此外，结肠和肝脏中的组织驻留记忆T细胞（TRM）表现出不同的转录谱。值得注意的是，我们的分析表明，肝脏微环境中富集的因子可能会影响结肠固有层TRM的表型。这种整合的单细胞分析描绘了T细胞在肠-肝-血轴上的克隆分布和适应性，突出了肝脏在塑造结肠免疫方面的潜在作用。
