The extra-islet pancreas supports autoimmunity in human type 1 diabetes
Year: 2024
Type: preprint
Abstract: In autoimmune type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans — islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular programs outside islets to insulitis is unclear. Here, using CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples, we simultaneously examine islet and extra-islet inflammation in human T1D. We identify four sub-states of inflamed islets characterized by the activation profiles of CD8 + T cells enriched in islets relative to the surrounding tissue. We further find that the extra-islet space of lobules with extensive islet-infiltration differs from the extra-islet space of less infiltrated areas within the same tissue section. Finally, we identify lymphoid structures away from islets enriched in CD45RA + T cells — a population also enriched in one of the inflamed islet sub-states. Together, these data help define the coordination between islets and the extra-islet pancreas in the pathogenesis of human T1D.
Source: eLife
DOI: 10.7554/elife.100535
Authors: Graham L Barlow, Christian M Schürch, Salil S Bhate, Darci J Phillips, Arabella Young, Shen Dong, Hunter A Martinez, Gernot Kaber, Nadine Nagy, Sasvath Ramachandran, Janet Meng, Eva Korpos, Jeffrey A Bluestone, Garry P Nolan, Paul L Bollyky
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Leona M. and Harry B. Helmsley Charitable Trust, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Tissue Cytokine Sequestration and Immune Regulation in Autoimmunity, G1154828164, G1205372580, G1838830638, G2079217183, G2177221272, G2294560402, The Cellular Geography of Therapeutic Resistance in Cancer, G3391965770, G4484938617, G4643321680, Hyper-parameter 3D imaging of the bone marrow hematopoietic stem cell niche in leukemia and stress hematopoiesis by co-detection of expression (CODEX), Modeling the Role of Lymph Node Metastases in Tumor-Mediated Immunosuppression, G844559411, Deep phenotyping of the tumor microenvironment in hematological cancers by CODEX hyper-parameter tissue imaging, The Lung PCA: A Multi-Dimensional Atlas of Pulmonary Premalignancy, G9000306696, Stanford Diabetes Research Center, Molecular and Cellular Immunobiology
OpenAlex ID: W4402573140