TNF and rheumatoid arthritis: We have previously shown that macrophages from human RA joints exhibit a transcriptomic and phenotypic proinflammatory polarization profile that resembles that of granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages (GM-MØ) (20) and that MTX conditions macrophages towards the acquisition of a state of tolerance that renders them less responsive to TLR ligands, TNFα, and RA synovial fluid (21, 22).