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

Miguel A. Medina-Serpas; Maigan Brusko; Gregory J. Golden; Martha Campbell‐Thompson; Trevor Rogers; Shay Reardon; Amanda L. Posgai; Rhonda L. Bacher; Eline T. Luning Prak; C Liu; Klaus H. Kaestner; Ali Naji; Michael R. Betts; Lauren M. McIntyre; Mark A. Atkinson; Todd M. Brusko

doi:10.1016/j.celrep.2026.117144

ImmunologyCell ReportsMar 23, 2026

Peer-reviewed journal article

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

Miguel A. Medina-Serpas iD, Maigan Brusko iD, Gregory J. Golden iD, Martha Campbell‐Thompson iD, Trevor Rogers, Shay Reardon, Amanda L. Posgai iD, Rhonda L. Bacher iD, Eline T. Luning Prak iD, C Liu, Klaus H. Kaestner iD, Ali Naji iD, Michael R. Betts iD, Lauren M. McIntyre iD, Mark A. Atkinson iD, Todd M. Brusko iD

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Abstract

This study explores the inflammatory response observed in pancreata and pancreatic lymph node (pLN) samples obtained throughout the natural history of type 1 diabetes (T1D) including non-diabetic individuals and non-diabetic autoantibody positive individuals with high susceptibility using spatial transcriptomics (ST). Integration of ST with public single-cell RNA sequencing data enabled interrogation of transcriptional alterations in T1D pathogenesis across both tissues and cellular scales. In the T1D pancreas, we observed global upregulation of multiple inflammation-associated transcripts, including regenerating islet-derived (REG) family genes, complement factor 3 (C3), SOD2, and OLFM4, and highlighted cellular candidates potentially contributing to these signatures. Within the T1D pLN, we observed spatially restricted upregulation of lymphotoxin-{beta} (LTB) alongside follicular dendritic cell (FDC)-associated transcripts including FDCSP, CLU, and FCER2. Collectively, these findings highlight distinct inflammation signatures in the pancreas and regional pLN which can help inform the development of future therapeutic interventions.