2457) prevented joint erosion when they crippled a member of the TNF receptor superfamily, Death Receptor 3 (DR3), by blocking its ligand, TL1A.
Patients with rheumatoid arthritis are more likely to have extra copies of the gene that codes for DR3. A causative role for DR3 in disease pathology, however, had not been shown. Bull et al. now find that mice lacking DR3 are freed from the bone damage usually caused by antigen-induced arthritis. And blocking TL1A curtailed the bone erosion typical of collagen-induced arthritis in mice.
Back in the dish, the team investigated how this receptor–ligand pair might induce bone destruction in humans. They found that the addition of TL1A to ordinary monocytes from human blood enhanced the generation of bone-resorbing osteoclasts. Although how TL1A leads to osteoclast differentiation is not yet clear, its DR3 receptor is known to activate NFκB, which is required for osteoclast formation.
A few stones remain unturned in the hunt for vandals, as obstructing TL1A didn't eliminate bone destruction altogether. Still, the researchers point out that the anti-TL1A antibody did ameliorate much of the damage.