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 <i>NFKB1</i> and <i>BACH2</i>, 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 <i>NFKB1-BACH2</i>-expressing CD4 T cells may lead to therapeutic avenues for preventing or delaying T1D onset.
Authors
- Golnaz Vahedi (ORCID: https://orcid.org/0000-0002-2249-8247)
- Klaus H. Kaestner (ORCID: https://orcid.org/0000-0002-1228-021X)
- Isabelle Johnson (ORCID: https://orcid.org/0009-0006-0357-6832)
- Aditi Chandra (ORCID: https://orcid.org/0000-0002-2053-163X)
- Maria Fasolino
- Robert B. Faryabi (ORCID: https://orcid.org/0000-0002-7931-2175)
- Priyadarshini Rai (ORCID: https://orcid.org/0000-0002-5684-3993)
- Atishay Jay (ORCID: https://orcid.org/0000-0003-3739-6726)
- Vung Lian (ORCID: https://orcid.org/0009-0004-8069-3704)
- Michael A. Silverman (ORCID: https://orcid.org/0000-0002-7876-4399)
- Yeqiao Zhou (ORCID: https://orcid.org/0000-0002-9422-6902)
- Susan Rostami (ORCID: https://orcid.org/0009-0004-4791-9281)
- Yanjing Li (ORCID: https://orcid.org/0000-0002-6036-547X)
- Ali Naji (ORCID: https://orcid.org/0000-0002-6926-3306)
- Wei Wang (ORCID: https://orcid.org/0000-0003-3344-0080)
- Chengyang Liu (ORCID: https://orcid.org/0000-0001-9812-1676)
- Ming Yu (ORCID: https://orcid.org/0000-0001-9935-4412)
- Maryam Abedi (ORCID: https://orcid.org/0000-0001-9724-9985)
- Z. Min (ORCID: https://orcid.org/0000-0001-7102-653X)
Institutions
- Children's Hospital of Philadelphia (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-11-21
- DOI
- https://doi.org/10.1126/sciimmunol.adz0472
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00