REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1630507
This article is part of the Research TopicInnate Immunity and Metabolic Disorders: Molecular Mechanisms and Therapeutic ImplicationsView all articles
Interactions Between Islet-Resident Macrophages and β Cells in Diabetes
Provisionally accepted
- 1Department of Pediatrics , Shengjing Hospital of China Medical University, Shenyang, China
- 2Department of Public health , Shengjing Hospital of China Medical University, Shenyang, China
- 3Department of Thoracic surgery, Shengjing Hospital of China Medical University, Shenyang, China
- 4Department of Emergency , Shengjing Hospital of China Medical University, Shenyang, China
- 5Department of Cardiology , Shengjing Hospital of China Medical University, Shenyang, China
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In diabetes, islet-resident macrophages (IRMs) and β cells engage in multifaceted interactions through diverse signaling pathways and cell-cell contact within the islet microenvironment, jointly shaping both homeostasis and disease progression. This review first outlines the origin, renewal dynamics, and phenotypic heterogeneity of IRMs, highlighting their essential roles in maintaining metabolic and immunological homeostasis under physiological conditions. We then emphasize the dual role of IRMs in type 1 and type 2 diabetes (T1DM and T2DM): in T1DM, they drive autoimmunity via antigen presentation and pro-inflammatory cytokine secretion; in T2DM, metabolic stress induces M1 polarization, exacerbating β cell dysfunction and dedifferentiation. We further explore molecular mechanisms modulating IRM-β cell crosstalk, including neuro-immune-endocrine networks (e.g., α1-adrenergic signaling), Interleukin-1 Beta (IL-1β) feedback loops, and the C-X-C Motif Chemokine Ligand 16 (CXCL16)/ Oxidized Low-Density Lipoprotein (OxLDL) axis. The paracrine actions of growth factors such as PDGF, VEGF-A, and IGF-1 in β cell proliferation and regeneration are also reviewed. Additionally, novel therapeutic targets, such as G Protein-Coupled Receptor 132 (GPR132) and exosomal miRNAs, offer promising strategies to precisely regulate macrophage polarization and protect β cells. Finally, we discuss the application of advanced technologies-such as single-cell sequencing and intravital imaging-in deciphering dynamic IRM-β cell interactions and highlight the prospects of modulating islet macrophage phenotypes to restore metabolic and immune balance in future research and clinical translation.
Keywords: islet-resident macrophages, β cells, diabetes, cell-cell interaction, Immunometabolism, therapeutic targets
Received: 17 May 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 张, Meng, Xi, Li, Chen, Li, Dong and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Na Wu, Department of Pediatrics , Shengjing Hospital of China Medical University, Shenyang, China
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