In summary, we established KLF4 to be a TNF-α-induced transcription factor that regulates expression of the key proinflammatory cytokine IL-6 in RA FLSs through both direct promoter activation and interaction with NF-κB. These results indicate that KLF4, which is induced by proinflammatory stimuli, can regulate FLSs activation and RA-associated inflammation. Here, NFKB1 is linked to rheumatoid arthritis.