Citations 1
Spatial multiomics of human hepatic lymph nodes reveals early APC bifurcation in liver transplant rejection
Nguyen, Justin H. , Ashraf, Humza, Moore, Raymond M. , Sherman, William H., Ma, Yaohua , Embretsen, Mattias , Cogen, Davitte , Kachergus, Jennifer M., Thompson, Cheryl L. , Killeen, Heather, Nakhleh, Raouf E. , Thompson, E. Aubrey , Knutson, Keith L. , Ashraf, Humza, Sherman, William, Thompson, Cheryl, Killeen, Heather E., Wang, Chen , Markovic, Svetomir N. , Knutson, Keith L.
No container title available | October 28, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract The highest risk for liver allograft rejection is within the first weeks to months after a liver transplant; however, while later-stage mechanisms are well described, the initial window at the moment of alloantigen influx (e.g., ~ 1 h post-reperfusion) remains unmapped. T-cell priming is initiated in lymph nodes, yet these sites are rarely profiled in humans and their relationship to rejection risk is unclear. To address this gap, we profiled paired pre- and ~ 1 h post-reperfusion hepatic draining lymph nodes from liver transplant recipients using multiplexed immunofluorescence and GeoMx whole-transcriptome profiling to identify features that predict rejection versus non-rejection. Early after reperfusion, CD4 + and CD8 + T cells became proximal to macrophages in rejection compared to dendritic cells in non-rejection, which also displayed an immunoregulatory-leaning profile marked by PD-1, IDO1, and CD39, suggesting that macrophages and dendritic cells differentially influence early T-cell alloimmunity. These results provide nodal targets for precise immune modulation.