Since we observed a misbalance between immunosuppressive and immunostimulatory Mφs in human and murine arthritic joints, we devised a new strategy for RA treatment based on targeted delivery of a novel methotrexate (MTX) formulation to the immunosuppressive FRβ+CD39+CD73+ Mφs, which boosts adenosine production and curtails the dominance of proinflammatory Mφs. The gene discussed is ENTPD1; the disease is rheumatoid arthritis.