Blocking YY1 action with YY1 shRNA lentivirus ameliorated disease progression in CIA mice. Histological examination showed ↓ leukocyte infiltration, cartilage destruction, and bone erosion in treated mice.YY1 blockade significantly ↓ the inflammatory score in CIA mice and inhibited T cell proliferation in response to CII antigen.Blocking YY1 led to ↓ IL-6 production and JAK/Stat in PBMCs from RA patients.YY1 blockade led to ↓ Th17 population in CIA mice. The gene discussed is IL6; the disease is rheumatoid arthritis.