It is highly possible that loss of Smad7 in CD4+ T cells may impair the balance of TGF-β/Smad signaling with overreactive Smad3, which, together with IL-6, promotes Th17 response, resulting in the imbalance of Th17/Treg in RA patients. The gene discussed is TGFB1; the disease is rheumatoid arthritis.