Spatial transcriptomics from pancreas and local draining lymph node tissue reveals a lymphotoxin-β signature in human type 1 diabetes

作者：Miguel A. Medina-Serpas, Maigan Brusko, Gregory J. Golden, M. Campbell-Thompson, Trevor Rogers, Shay Reardon, Amanda L. Posgai, Rhonda Bacher, Eline T. Luning Prak, C Liu, Klaus H. Kaestner, Ali Naji, Michael R. Betts, Lauren M. McIntyre, Mark A. Atkinson, Todd M. Brusko · 发表于：Cell Reports · 年份：2026 · DOI：10.1016/j.celrep.2026.117144 · 被引用次数：2 · 研究领域：Diabetes and associated disorders、T-cell and B-cell Immunology、Pancreatic function and diabetes

This study explores the inflammatory response observed in the pancreas and pancreatic lymph nodes (pLNs) during the natural history of type 1 diabetes (T1D). Using multicell-resolution spatial transcriptomics (ST), we profile individuals without diabetes (ND), at-risk autoantibody-positive (AAb+) individuals, and T1D donors. In the T1D pancreas, we observed global upregulation of inflammation-associated transcripts, including REG family genes, C3, SOD2, and OLFM4. In the T1D pLN, LTB was significantly upregulated within the lymphoid follicles. Using an orthogonal subcellular-resolution ST platform on an independent donor set, we identified follicular B cells as the primary source of LTB in the pLN and observed increased LTB expression in lymphocytes in insulitic lesions proximal to CCL19/CCL21-expressing endothelium. Collectively, these findings highlight lymphotoxin-β and downstream chemokine signatures in the pancreatic lymphatics as well as within the insulitic lesion, which can inform future therapeutic interventions.