Myeloid-Specific Heparanase Aggravates Insulitis in Type 1 Diabetes via Heparan Sulfate Fragment-Dependent Amplification of Macrophage Polarization.
basic_science · Level V
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- Record sourced from PubMed, PMID 42536487.
- Also identified by DOI 10.2337/db26-0365.
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Abstract
The role of the heparanase (HPSE)-heparan sulfate (HS) axis in type 1 diabetes remains incompletely defined. We examined whether myeloid-derived HPSE drives islet inflammation, how HS fragments influence macrophage polarization, and whether pharmacological inhibition is protective. We found that myeloid HPSE disrupts the intraislet HS barrier and that the resulting HS fragments potentiate interferon-γ-STAT1 signaling to promote proinflammatory macrophage polarization. Genetic or pharmacological inhibition of HPSE preserved islet integrity and ameliorated diabetes, identifying this pathway as a potential therapeutic target in type 1 diabetes.