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 Bacher; Eline T Luning Prak; Chengyang 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

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

Cell Rep. 2026 Mar 23;45(4):117144. doi: 10.1016/j.celrep.2026.117144. Online ahead of print.

Authors

Miguel A Medina-Serpas¹, Maigan Brusko¹, Gregory J Golden², Martha Campbell-Thompson¹, Trevor Rogers¹, Shay Reardon³, Amanda L Posgai¹, Rhonda Bacher⁴, Eline T Luning Prak⁵, Chengyang Liu⁶, Klaus H Kaestner⁷, Ali Naji⁸, Michael R Betts², Lauren M McIntyre⁹, Mark A Atkinson¹⁰, Todd M Brusko¹¹

Affiliations

¹ Diabetes Institute, University of Florida, Gainesville, FL 32610, USA; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
² Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
³ Department of Computer Information Science and Engineering, University of Florida, Gainesville, FL, USA.
⁴ Diabetes Institute, University of Florida, Gainesville, FL 32610, USA; Department of Biostatistics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
⁵ Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶ Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁷ Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁸ Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁹ Department of Biostatistics, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
¹⁰ Diabetes Institute, University of Florida, Gainesville, FL 32610, USA; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
¹¹ Diabetes Institute, University of Florida, Gainesville, FL 32610, USA; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA. Electronic address: tbrusko@ufl.edu.

Abstract

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.

Keywords: CP: immunology; CP: metabolism; autoantibodies; autoimmunity; human; islet cells; lymph node; lymphotoxin-β; pancreas; spatial transcriptomics; type 1 diabetes.

Abstract

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