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CD84 Determines Differential Fates of Pro-fibrotic Macrophages [RNA-seq]

ABSTRACT: To define the transcriptional effects of CD84 engagement, bone marrow-derived macrophages (BMDMs) from wild-type and Cd84-knockout mice were stimulated with mouse recombinant CD84 (rCD84) and analyzed by bulk RNA sequencing. CD84 engagement induced inflammatory, chemotactic, survival, and adhesion-related gene programs in wild-type macrophages, whereas these responses were markedly reduced by Cd84 deletion. Pathway analysis highlighted cytokine activity, inflammatory responses, leukocyte chemotaxis, focal adhesion, TNF signaling, and JAK/STAT signaling. These findings establish CD84 as a key regulator of macrophage activation and pro-fibrotic transcriptional programming.

ORGANISM(S): Mus musculus

PROVIDER: GSE344928 | GEO | 2026/09/25

REPOSITORIES: GEO

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Project description:Extracellular vesicles derived from induced pluripotent stem cells (iPSC EVs) have immunoregulatory potential with the ability to alter monocyte-derived macrophages. Macrophages function in the propagation and resolution of inflammation which is mediated by their phenotype. Macrophages are an ideal therapeutic target as modulating their phenotype towards an anti-inflammatory pro-resolving state may be beneficial in chronic inflammatory diseases such as atherosclerosis. Macrophages are naturally phagocytotic cells and readily take up iPSC EVs however the contents of iPSC EVs and their effects on macrophages are poorly understood. Here iPSC EVs were characterized and analysed by mass-spectrometry based proteomics and a targeted microRNA (miR) panel. Their immunomodulatory effects on macrophages were assessed and a monocyte transmigration assay was used to assess the chemotactic potency of the secretome from iPSC EV treated macrophages. Proteomic analysis on iPSC EVs identified Podocalyxin-like protein 1 (PODXL1), Insulin (INS) and Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 3 (SLC2A3) as the most abundant proteins unique to the iPSC EVs when compared to control NT-2 EVs. Notably, thioredoxin and peroxiredoxin related proteins were detected. miR-302d-3p was the most abundant miR in these iPSC EVs. miR-25-3p, previously reported to alter the macrophage phenotype, was significantly increased in comparison to the control NT-2 EVs. iPSC EVs increased expression of the anti-inflammatory associated MRC1 and miR-21 in human primary macrophages and decreased monocyte chemoattractant protein1 (MCP-1). Mass spectrometry based proteomics revealed that treated macrophages had decreased levels of secretory proteins, some of which have chemotactic properties, these included Azurocidin 1 (AZU1), Growth Differentiation Factor 15 (GDF15), and Ribosomal Protein S19 (RPS19). There was a decrease in monocyte transmigration towards conditioned media from macrophages treated with iPSC EVs. Collectively this study provides insights into the protein content and miR cargo of iPSC EVs and highlights their capacity to inhibit chemotactic proteins in macrophages and upregulate MRC1.

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CD84 Determines Differential Fates of Pro-fibrotic Macrophages [RNA-seq]

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