Furthermore, there is strong evidence of a lack of tolerance in RA, which may be ascribable to regulatory-T-cell impairment at the time of TLR2 stimulation with TLR1 or TLR6 co-engagement by ligands, allowing pathogenic immune cells to escape from normal regulatory mechanisms and to trigger or exacerbate arthritis. The gene discussed is TLR1; the disease is arthritic joint disease.