An islet-resident macrophage antioxidant program preserves β cell physiology

Pancreatic islet-resident macrophages (IRMs) display an activated phenotype and contribute to islet development and remodeling, yet their origin, heterogeneity, and functional roles remain poorly understood. Using complementary fate-mapping systems, we show that, in adult mice, around half of IRMs originate from circulating monocytes and undergo minimal turnover. Integrated multiple single-cell RNA sequencing analyses of mouse and human islets identified four major IRM cell states that collectively reveal their inflammatory and metabolic activation. Among these, a transcriptional program driven by the cystine-glutamate antiporter SLC7A11 and enriched in CD9<sup>high</sup> IRMs was associated with enhanced antioxidant defense, mitochondrial activity, and iron-lipid metabolic pathways. We found that <i>Slc7a11</i>-expressing IRMs preserve β cell redox homeostasis and insulin secretion, both at baseline and under stress. These findings position IRMs as specialized immune sentinels in the endocrine pancreas and identify SLC7A11 as a key macrophage-intrinsic safeguard against oxidative stress, with broad implications for islet resilience and metabolic health.

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Publication Details

Journal
Science Immunology
Published
2025-11-14
DOI
https://doi.org/10.1126/sciimmunol.adz5181
Citations
3
Primary Topic
Pancreatic function and diabetes
Type
article
Field-Weighted Citation Impact
6.02
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article

An islet-resident macrophage antioxidant program preserves β cell physiology

Ann Massie, Martine Ropert, Nicolas Venteclef, Laura G. Baudrin et al.
3 citations
Science Immunology
Pancreatic function and diabetes
6.02
article

An islet-resident macrophage antioxidant program preserves β cell physiology

Ann Massie, Martine Ropert, Nicolas Venteclef, Laura G. Baudrin, David Alejandro Bejarano, Zhaoyuan Liu, Gamze Ates, Ivan Nemazanyy, Amélie Grosjean, Florent Ginhoux, Kevin Mulder, Jean–François Gautier, Marc Diedisheim, Joyceline Cuenco, Clément Materne, Ahmed Hamaï, Élise Dalmas, Claire Leveau, Sylvain Baulande, Andreas Schlitzer, Jarne Walckiers, Ana Sofia Gonçalves, Marie‐Laure Island, Audrey Le Guernic, Aude Jalon
article en
3 citations

Abstract

Pancreatic islet-resident macrophages (IRMs) display an activated phenotype and contribute to islet development and remodeling, yet their origin, heterogeneity, and functional roles remain poorly understood. Using complementary fate-mapping systems, we show that, in adult mice, around half of IRMs originate from circulating monocytes and undergo minimal turnover. Integrated multiple single-cell RNA sequencing analyses of mouse and human islets identified four major IRM cell states that collectively reveal their inflammatory and metabolic activation. Among these, a transcriptional program driven by the cystine-glutamate antiporter SLC7A11 and enriched in CD9<sup>high</sup> IRMs was associated with enhanced antioxidant defense, mitochondrial activity, and iron-lipid metabolic pathways. We found that <i>Slc7a11</i>-expressing IRMs preserve β cell redox homeostasis and insulin secretion, both at baseline and under stress. These findings position IRMs as specialized immune sentinels in the endocrine pancreas and identify SLC7A11 as a key macrophage-intrinsic safeguard against oxidative stress, with broad implications for islet resilience and metabolic health.

Science ImmunologyVol. 10(113)
Centre National de la Recherche Scientifique (FR), Vrije Universiteit Brussel (BE), University of Bonn (DE), Inserm (FR), Shanghai Jiao Tong University (CN), Université Paris Cité (FR), Université Paris Sciences et Lettres (FR), Institut Gustave Roussy (FR), Université Rennes 2 (FR), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Centre de Recherche des Cordeliers (FR), Hôpital Lariboisière (FR), Hôpital Pontchaillou (FR), Foie, Métabolisme, Cancer (FR), Centre Hospitalier Universitaire de Rennes (FR), Université de Rennes (FR)
Openalex Percentile: Top 3%
Pancreatic function and diabetes
6.02
DOISourceOpenAlex
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