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Article Abstract
Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of Il34 in mice (IL-34) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34 mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, ex vivo murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of Il-34 mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.
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| http://dx.doi.org/10.1016/j.trsl.2025.07.002 | DOI Listing |
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