Abstract
The subcutaneous fascia (scFascia) is a widely distributed connective tissue, yet its contribution to systemic responses during visceral inflammation remains insufficiently defined. In the rat model of Salmonella-induced dysentery, scRNA-seq of scFascia combined with deep neural network (DNN)-based nonlinear feature discovery revealed transcriptional alterations indicative of Warburg-like reprogramming in macrophages (MPs), accompanied by reduced activity of the citrate cycle. Cd34 + /Pdgfra+ telocytes (CPTCs) regulated MP differentiation and proliferation through Wnt/Fgf signaling, suggesting a pathological communication pattern between scFascia and visceral organs, termed the fascia-visceral inflammatory crosstalk pattern (FVICP). PySCENIC analysis showed increased activity of transcription factors Fosl1, Nfkb2, and Atf4, modulated by CPTC signaling to MPs, leading to downregulation of aerobic respiration and upregulation of the cell cycle, DNA replication, and transcription. Co-culture assays demonstrated that CPTCs suppressed the pro-inflammatory activity of MPs by transcriptionally downregulating TLR4 and CPT1A while upregulating ATF4, and enhanced anti-inflammatory potential via post-transcriptional MTOR upregulation. These findings highlight the role of scFascia in immunomodulation and metabolic reprogramming during visceral inflammation, emphasizing its contribution to systemic homeostasis.