Trem2 and Olfr2 Nexus determines the inflammatory phenotype of foamy macrophages Trem2 and Olfr2 nexus determines the inflammatory phenotype of foamy macrophages 4023
Year: 2025
Type: article
Abstract: Description Atherosclerosis is a lipid-driven immuno-metabolic and inflammatory disorder characterized by plaque formation in the arterial intima, primarily due to the accumulation of modified low-density lipoproteins (LDL) such as oxidized LDL. After oxLDL exposure macrophages acquire a lipid-loaded “foamy” phenotype characterized by the expression of Trem2, which modulate oxLDL uptake, esterification, and storage. When overwhelmed, foamy macrophages can switch to a proinflammatory state, leading to disease progression. This mechanism is still unknown. Here, we described that Olfr2, whose depletion has been shown to be protective in atherosclerosis, is involved in the proinflammatory switch of foam cells that leads to atherosclerosis progression. We found that the lack of Olfr2 in BMDMs mediates less oxLDL accumulation, significantly reducing the lipid marker (BODIPY) signal compared to WT. Gene expression analysis showed significant upregulation of oxLDL processing genes like Abcg1, Pparg, and Trem2 and downregulation of Srebf1 as well as upregulation of anti-inflammatory gene like Il10 in oxLDL-treated Olfr2 KO BMDMs compared to WT BMDMs. Upregulation of Trem2 in Olfr2 KO BMDMs after oxLDL incubation was confirmed by flow cytometry. Similarly, citral, a known Olfr2 inhibitor, upregulated Trem2 after oxLDL incubation. Delineating Olfr2 and Trem2 pathways interplay might help to identify a potential target to lower the disease burden of atherosclerosis in humans. Funding Sources AHA Career developement Award to MO; Augusta Univesrity Start-Up funds to MO Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)
Source: The Journal of Immunology
Authors: Adil Ijaz, Sabrina Robichaud, Adil Rasheed, Natalya Resto-Trujillo, Marco Orecchioni
Institution: Augusta University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416448928
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