ArticleJCI insight2024
Adrenal gland macrophages regulate glucocorticoid production through Trem2 and TGF-β.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Adrenal rather than central dysfunction limits hypothalamic-pituitary-adrenal axis recovery after chronic glucocorticoid treatment in male mice.Endocrinology · 2026Article
- Depletion and replacement of tissue-resident macrophages in mice with germ-line deletion of a conserved enhancer in the Csf1r locus.Development (Cambridge, England) · 2026Article
- Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments.International journal of molecular sciences · 2026Review
- Adrenal Gland Macrophage-derived TGF-β Governs Vascular Permeability to Drive Monocyte Recruitment during Stress.bioRxiv : the preprint server for biology · 2026Article
- Macrophage regulation of hypothalamic-pituitary-adrenal and gonadal axis homeostasis and hormonal output.Biomedical journal · 2026Review
- The Immune Biology of the Adrenal Gland Microenvironment and Its Role in Metastatic Progression.International journal of molecular sciences · 2026Review
- TREM2-driven peripheral macrophage regulation in inflammatory diseases: implications extending beyond neurological disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Mechanisms of Innate Immune Modulation by High-Fat Diet: Implications for Obesity and Asthma.Current allergy and asthma reports · 2025Review
- Identification of conserved and tissue-restricted transcriptional profiles for lipid associated macrophages.Communications biology · 2025Article
- Multiomics analysis unveils the cellular ecosystem with clinical relevance in aldosterone-producing adenomas withProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Lipid metabolism in the adrenal gland.Frontiers in endocrinology · 2025Review
- Identification of conserved and tissue-restricted transcriptional profiles for lipid associated macrophages (LAMs).bioRxiv : the preprint server for biology · 2024Article
- Developmental programming of tissue-resident macrophages.Frontiers in immunology · 2024Review
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Authors and funding
15 authors.
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Abstract
Glucocorticoid synthesis by adrenal glands (AGs) is regulated by the hypothalamic-pituitary-adrenal axis to facilitate stress responses when the host is exposed to stimuli. Recent studies implicate macrophages as potential steroidogenic regulators, but the molecular mechanisms by which AG macrophages exert such influence remain unclear. In this study, we investigated the role of AG macrophages in response to cold challenge or atherosclerotic inflammation as physiologic models of acute or chronic stress. Using single-cell RNA sequencing, we observed dynamic AG macrophage polarization toward classical activation and lipid-associated phenotypes following acute or chronic stimulation. Among transcriptional alterations induced in macrophages, triggering receptor expressed on myeloid cells 2 (Trem2) was highlighted because of its upregulation following stress. Conditional deletion of macrophage Trem2 revealed a protective role in stress responses. Mechanistically, Trem2 deletion led to increased AG macrophage death, abolished the TGF-β-producing capacity of AG macrophages, and resulted in enhanced glucocorticoid production. In addition, enhanced glucocorticoid production was replicated by blockade of TGF-β signaling. Together, these observations suggest that AG macrophages restrict steroidogenesis through Trem2 and TGF-β, which opens potential avenues for immunotherapeutic interventions to resolve stress-related disorders.
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