Joint profiling of gene expression and chromatin accessibility in pancreatic lymph nodes and spleens in human type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreas. While current therapies focus on managing the disease, a deeper understanding of the underlying molecular mechanisms is crucial for developing disease-modifying interventions. In this study, we conducted a comprehensive analysis of gene expression and chromatin accessibility in nearly 1 million immune cells from the pancreatic lymph nodes and spleens of 43 individuals with and without T1D. We found a distinct subset of CD4 T cells specifically present in the pancreatic lymph nodes of organ donors representing the active disease stage. These cells exhibited elevated activity of NFKB1 and BACH2, along with extensive chromatin remodeling associated with these transcription factors, which we also corroborated in a mouse model of T1D. A better understanding of these NFKB1-BACH2-expressing CD4 T cells may lead to therapeutic avenues for preventing or delaying T1D onset.