Adrenal gland macrophages regulate glucocorticoid production through Trem2 and TGF-β

• DOI: 10.1172/jci.insight.174746
• Publication Date: 2024-06-13T16:01:04Z
• Authors: Yingzheng Xu; Michael T. Patterson; Bastien Dolfi; Alisha Zhu; Adeline Bertola; Patricia R. Schrank; Alexandre Gallerand; Ainsley E. Kennedy; Hannah Hillman; Lynn Dinh; Sia Shekhar; Samuel Tollison; Tyler D. Bold; Stoyan Ivanov; Jesse W. Williams
• Keywords: TREM2

Glucocorticoid synthesis by adrenal glands (AGs) is regulated the hypothalamic-pituitary-adrenal axis to facilitate stress responses when host exposed stimuli. Recent studies implicate macrophages as potential steroidogenic regulators, but molecular mechanisms which AG exert such influence remain unclear. In this study, we investigated role of in response cold challenge or atherosclerotic inflammation physiologic models acute chronic stress. Using single-cell RNA sequencing, observed dynamic macrophage polarization toward classical activation and lipid-associated phenotypes following stimulation. Among transcriptional alterations induced macrophages, triggering receptor expressed on myeloid cells 2 (Trem2) was highlighted because its upregulation Conditional deletion Trem2 revealed a protective responses. Mechanistically, led increased death, abolished TGF-β-producing capacity resulted enhanced glucocorticoid production. addition, production replicated blockade TGF-β signaling. Together, these observations suggest that restrict steroidogenesis through TGF-β, opens avenues for immunotherapeutic interventions resolve stress-related disorders.