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Transcriptomic characterization of human pancreatic CD206- and CD206 + macrophages
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer Immunotherapy.ORCID iD: 0000-0003-1455-2802
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer Immunotherapy. Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID iD: 0000-0002-8524-9547
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer Immunotherapy.ORCID iD: 0000-0002-3835-5523
2025 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 15, no 1, article id 12037Article in journal (Refereed) Published
Abstract [en]

Macrophages reside in all organs and participate in homeostatic- and immune regulative processes. Little is known about pancreatic macrophage gene expression. In the present study, global gene expression was characterized in human pancreatic macrophage subpopulations. CD206- and CD206 + macrophages were sorted separately from pancreatic islets and exocrine tissue to high purity using flow cytometry, followed by RNA-seq analysis. Comparing CD206- with CD206 + macrophages, CD206- showed enrichment in histones, proliferation and cell cycle regulation, glycolysis and SPP1-associated immunosuppressive polarization while CD206 + showed enrichment in complement and coagulation-, IL-10 and IL-2RA immune regulation, as well as scavenging-related gene sets. Comparing islet CD206- with exocrine CD206-, enrichments in islet samples included two sets involved in immune regulation, while enrichments in exocrine samples included sets related to extracellular matrix and immune activation. Fewer differences were found between CD206 + macrophages, with enrichments in islet samples including two IL2-RA related gene sets, while enrichments in exocrine samples included sets related to extracellular matrix and immune activation. Comparing macrophages between individuals with normoglycemia, elevated HbA1c or type 2 diabetes, only a few diverse differentially expressed genes were identified. This work characterizes global gene expression and identifies differences between CD206- and CD206 + macrophage populations within the human pancreas.

Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 15, no 1, article id 12037
Keywords [en]
Human pancreas, Pancreatic macrophages, Diabetes, Transcriptomics, Pancreatic Islets
National Category
Cell and Molecular Biology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-553405DOI: 10.1038/s41598-025-96313-yISI: 001463208500022PubMedID: 40199933OAI: oai:DiVA.org:uu-553405DiVA, id: diva2:1947898
Funder
Uppsala UniversityAvailable from: 2025-03-27 Created: 2025-03-27 Last updated: 2025-04-29Bibliographically approved
In thesis
1. Studies of human pancreatic innate immunity and microvasculature in the context of diabetes pathophysiology
Open this publication in new window or tab >>Studies of human pancreatic innate immunity and microvasculature in the context of diabetes pathophysiology
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diabetes is a set of chronic diseases characterized by hyperglycemia and pancreatic dysfunction. The pancreas consists of two tissue compartments with highly distinct functions – hormone-producing islets of Langerhans and acinar tissue with an exocrine function. Improved understanding of immune processes and stromal cells within the compartments of the pancreas may highlight important specializations, which could lead to novel insights into islet dysfunction in diabetes or islet transplantation. Thus, in this thesis the properties of pancreatic innate immunity and microvascular endothelial cells were compared between islet- and exocrine tissue from human organ donors. 

Enteroviral infection has been suggested to trigger development of type 1 diabetes. In paper I, the feasibility of using innate immunity viral sensor protein kinase R (PKR) as evidence of enteroviral infection in the pancreas was examined. A general PKR expression was found at protein and RNA level in islets and exocrine tissue under basal conditions, and in vitro infection of islets with enterovirus did not lead to distinct PKR expression. This suggests that PKR expression should not be used to corroborate enteroviral infection in the human pancreas. In paper II, gene expression profiles were generated and compared between microvascular endothelial cells (MVECs) from islets and exocrine tissue. Gene sets involved in vascular- and endothelial development were enriched in islet MVEC samples. This suggests increased vascular proliferation within islets, potentially consistent with tissue remodeling. In paper III, gene expression profiles were generated and analyzed in CD206- and CD206+ macrophages from islets and exocrine tissue. Gene sets involved in inflammation and glycolysis were enriched in CD206- macrophages, while gene sets involved in complement, scavenging and immune regulation were enriched in CD206+ macrophages. In comparisons between tissues, a few immune regulation-associated gene sets were enriched in islet macrophages while gene sets associated with proinflammatory functions and extracellular matrix were enriched in exocrine macrophages. 

The main findings in this thesis were that expression of PKR is poor evidence of viral infection in the pancreas, identification of islet-MVEC gene expression consistent with intraislet vascular remodeling, and a characterization of global gene expression in two subgroups of macrophages in islets and in exocrine tissue.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 67
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2147
Keywords
Islets of Langerhans, innate immunity, human pancreas, pancreatic microvasculature, pancreatic macrophages
National Category
Immunology in the Medical Area Cell and Molecular Biology Endocrinology and Diabetes
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-553409 (URN)978-91-513-2459-3 (ISBN)
Public defence
2025-05-27, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2025-05-05 Created: 2025-03-27 Last updated: 2025-05-05

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