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Efferocytic remodeling of pancreatic intra-islet macrophages by limited beta-cell death

ABSTRACT: The primary driver of Type I diabetes are the autoimmune T cells that destroy insulin-producing beta-cells within the islets of Langerhans in the pancreas. Pancreatic macrophages have also been variably linked to disease onset and progression. As macrophage-mediated removal of dying cells via ‘efferocytosis’ regulate tissue homeostasis and immune responses, we addressed whether efferocytosis by intra-islet macrophages influences the immune environment of pancreatic islets. Here, using a series of complementary omics-based and functional approaches, we identify a subset of anti-inflammatory intra-islet ‘efferocytic macrophages’ (e-Mac) within the pancreas of mice and humans. When limited beta-cell apoptosis is induced in vivo in wild type C57BL/6 mice and diabetic-prone NOD mice, islet macrophages adopt this e-Mac phenotype without an apparent increase in total intra-islet macrophage numbers. Strikingly, such induction of limited beta-cell apoptosis and increase in e-Mac numbers in NOD mice led to long-term suppression of autoimmune diabetes. These data advance a concept that efferocytosis-associated reprogramming of the islet macrophages and its subsequent influence on the adaptive immune response could be beneficial in modulating diabetic autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE304628 | GEO | 2025/08/09

REPOSITORIES: GEO

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Efferocytic remodeling of pancreatic intra-islet macrophages by limited beta-cell death [bulk_RNASeq_mouse]

Project description:The primary driver of Type I diabetes are the autoimmune T cells that destroy insulin-producing beta-cells within the islets of Langerhans in the pancreas. Pancreatic macrophages have also been variably linked to disease onset and progression. As macrophage-mediated removal of dying cells via ‘efferocytosis’ regulate tissue homeostasis and immune responses, we addressed whether efferocytosis by intra-islet macrophages influences the immune environment of pancreatic islets. Here, using a series of complementary omics-based and functional approaches, we identify a subset of anti-inflammatory intra-islet ‘efferocytic macrophages’ (e-Mac) within the pancreas of mice and humans. When limited beta-cell apoptosis is induced in vivo in wild type C57BL/6 mice and diabetic-prone NOD mice, islet macrophages adopt this e-Mac phenotype without an apparent increase in total intra-islet macrophage numbers. Strikingly, such induction of limited beta-cell apoptosis and increase in e-Mac numbers in NOD mice led to long-term suppression of autoimmune diabetes. These data advance a concept that efferocytosis-associated reprogramming of the islet macrophages and its subsequent influence on the adaptive immune response could be beneficial in modulating diabetic autoimmunity.

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