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

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 () family genes, complement factor 3 (), , and , and highlighted cellular candidates potentially contributing to these signatures.

A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair.