NicheNet-Based Dissection of CD14 ⁺ Monocyte Crosstalk with Memory CD4 ⁺ T Cells in Human PBMCs

Intercellular communication between monocytes and T cells is essential for immune regulation within peripheral blood mononuclear cells (PBMCs). To examine how CD14 ⁺ monocytes regulate memory CD4 ⁺ T cells at the gene expression level, we applied NicheNet to PBMC single-cell RNA-seq data. We performed quality control, normalization, principal component analysis, and UMAP-based visualization. CD14 ⁺ monocytes and memory CD4 ⁺ T cells were identified by canonical markers and designated as sender and receiver populations, respectively. NicheNet analysis revealed both classical cytokine signaling and checkpoint-like interactions. Prominent ligands included TNF, IFNG, IL10, and CXCL9, predicted to regulate inflammatory target genes through receptors such as TNFRSF1A/B and CXCR3. In addition, the SIRPG–CD47 axis emerged as a potential costimulatory pathway modulating T cell responses. These results suggest that monocytes regulate memory CD4 ⁺ T cells via a combination of inflammatory, costimulatory, and regulatory signals, providing mechanistic hypotheses for immune modulation in health and disease.