hTNFtg mice carry five copies of the hTNF transgene [54] and they spontaneously develop chronic polyarthritis, a disease similar to human RA; while they have been successfully used as drug testing platforms for anti-TNF therapeutics [55], SFs have been highlighted as the key driver cell type in this model of disease, as TNF/TNFR1 signaling in SFs is sufficient and necessary for the disease manifestation [56]. This evidence concerns the gene TNF and rheumatoid arthritis.