Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data

Clin Immunol. 2024 Mar 31:110199. doi: 10.1016/j.clim.2024.110199. Online ahead of print.ABSTRACTCell-cell communication is crucial for regulating signaling and cellular function. However, the precise cellular and molecular changes remain poorly understood in skin aging. Based on single-cell and bulk RNA data, we explored to assess the role of cell-cell ligand-receptor interaction in skin aging. We found that the macrophage migration inhibitory factor (MIF)/CD74 was significantly upregulated and frequent interactions were observed on fibroblasts in aged skin. Enrichment analysis and in vitro experiment revealed a close association of the activation of the MIF/CD74 with inflammatory pathways and immune response. Mechanistically, MIF/CD74 could significantly inhibit PPARĪ³ protein, which thus significantly increased the degree of senescence of fibroblasts, and significantly up-regulated the expression of senescence-associated secretory phenotype (SASP) factors and FOS gene. Therefore, our study revealed that MIF/CD74 inhibits the activation of the PPAR signaling pathway, subsequently inducing the production of SASP factors and the upregulation of FOS expression, which accelerated fibroblast senescence.PMID:38565329 | DOI:10.1016/j.clim.2024.110199
Source: Clinical Immunology - Category: Allergy & Immunology Authors: Source Type: research