In this study, we combined single-cell RNA-sequencing analysis, genetic approaches and intervention strategies to describe a fundamental suppression of SIGIRR on the C/EBPβ/TNF-α signaling axis in orchestrating rheumatoid inflammation in patients with RA and a monoarticular model of experimental arthritis in memory CD4 T cells. The gene discussed is CEBPB; the disease is rheumatoid arthritis.