FOLR2+ Macrophages as inflammatory brake remodel extracellular matrix and inhibit IL-6 cascading in psoriasis (PRJCA048098)
Psoriasis is a chronic skin disease currently lacking a cure, highlighting the need for new therapeutic targets. Our previous single-cell multi-omics analysis revealed a distinct macrophage subtype characterized by FOLR2 expression. Notably, FOLR2+ Macrophages were significantly reduced in psoriatic skin compared to healthy ones. Therefore, we constructed conditional knock-in of FOLR2 mice (lyz2cre-folr2f/f) to study its role in psoriasis development. Interestingly, macrophage-specific Folr2 knock-in mice showed significant symptom improvement. RNA-seq data confirmed a pronounced downregulation of extracellular matrix (ECM) organization in FOLR2+ Macrophages. Using single-cell transcriptomic data, we further demonstrated that biological functions of FOLR2+ Macrophages in both human and mice skin were closely linked to leukocyte activation and differentiation, particularly T cell-mediated immunity, and Fn1(Fibronectin)-Cd44 interactions, participating ECM organization of macrophages and T cell adhesion. In summary, our findings discovered that FOLR2+ Macrophages subset in psoriasis play a significant role, and revealed that the mechanism is closely associated with the regulation of extracellular matrix and T cell-mediated immunity.