Pericytes modulate islet immune cells and insulin secretion through Interleukin-33 production in mice

Guzel Burganova, Anat Schonblum, Lina Sakhneny, Alona Epshtein, Tomer Wald, Mika Tzaig, Limor Landsman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Introduction: Immune cells were recently shown to support β-cells and insulin secretion. However, little is known about how islet immune cells are regulated to maintain glucose homeostasis. Administration of various cytokines, including Interleukin-33 (IL-33), was shown to influence β-cell function. However, the role of endogenous, locally produced IL-33 in pancreatic function remains unknown. Here, we show that IL-33, produced by pancreatic pericytes, is required for glucose homeostasis. Methods: To characterize pancreatic IL-33 production, we employed gene expression, flow cytometry, and immunofluorescence analyses. To define the role of this cytokine, we employed transgenic mouse systems to delete the Il33 gene selectively in pancreatic pericytes, in combination with the administration of recombinant IL-33. Glucose response was measured in vivo and in vitro, and morphometric and molecular analyses were used to measure β-cell mass and gene expression. Immune cells were analyzed by flow cytometry. Resuts: Our results show that pericytes are the primary source of IL-33 in the pancreas. Mice lacking pericytic IL-33 were glucose intolerant due to impaired insulin secretion. Selective loss of pericytic IL-33 was further associated with reduced T and dendritic cell numbers in the islets and lower retinoic acid production by islet macrophages. Discussion: Our study demonstrates the importance of local, pericytic IL-33 production for glucose regulation. Additionally, it proposes that pericytes regulate islet immune cells to support β-cell function in an IL-33-dependent manner. Our study reveals an intricate cellular network within the islet niche.

Original languageEnglish
Article number1142988
JournalFrontiers in Endocrinology
StatePublished - 2023


  • Interleukin-33
  • beta-cell activity
  • islet vasculature
  • islets of Langerhans
  • pancreatic pericytes


Dive into the research topics of 'Pericytes modulate islet immune cells and insulin secretion through Interleukin-33 production in mice'. Together they form a unique fingerprint.

Cite this