Tolerogenic dendritic cells modulate macrophage inflammatory response in Ulcerative colitis: role of IL-1RN

Abstract Background Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease whose pathogenesis involves various immune cells. Measures that suppress the inflammatory responses of intestinal macrophages are considered crucial for improving ulcerative colitis. In recent years, research on tolerogenic dendritic cells (TolDCs) has highlighted the body’s intrinsic immune regulation mechanisms. This study aims to identify biomarkers associated with macrophages and TolDCs in ulcerative colitis (UC) and to validate the inhibitory effects of TolDCs on macrophage inflammatory responses. Methods Data pertaining to UC and TolDCs were procured from public databases. The single-cell data were subjected to high-dimensional weighted gene co-expression network analysis (hdWGCNA) to identify macrophage module genes. TolDCs-related genes, as well as differentially expressed genes (DEGs) in UC, were identified through differential expression analysis, and candidate genes were identified by finding the overlap among the three aforementioned sections. The identification of biomarkers was facilitated by machine learning and gene expression analyses. Notably, the nomogram was utilized to evaluate the diagnostic efficacy of the biomarkers. Subsequently, functional enrichment analysis, immune infiltration analysis, drug prediction analysis, and cell co-culture experiments were conducted for verification. Results IL-1RN and SERPINA1 were identified as biomarkers, with their expression found to be upregulated in UC samples. The nomogram developed using these biomarkers demonstrated good discriminative performance in differentiating between UC samples and normal control samples. Additionally, both IL-1RN and SERPINA1 exhibited substantial positive correlations with M0/1 macrophages (correlation coefficients (r) > 0.30, P < 0.001). Furthermore, cell co-culture experiments confirmed that TolDCs could reduce the expression of IL-1α, IL-1β, and TNF-α in macrophages through IL-1RN. Conclusion Our findings demonstrate that TolDCs suppress macrophage pro‑inflammatory cytokine expression via IL‑1RN, establishing IL‑1RN as a key functional mediator for UC, while SERPINA1 is proposed as a candidate diagnostic biomarker that may act upstream of IL‑1RN.