Signals from Rusty Joints

Perhaps you suffer from rheumatoid arthritis or your mother or an aunt does. The autoimmune disease, RA for short, affects one and a half million Americans, and most of them are women. Their immune system which protects them from infections also causes chronic inflammation that can damage organs, but especially flexible joints.

Scientists have been looking for ways to block this response and recently found one. Their work focused on a group of cells called macrophages. Macrophages are in every tissue in our body and are crucial to our immune response. Thus they're also in the synovial fluid which cushions our joints.

In people with RA, the macrophages in this lubricating fluid have elevated levels of a family of proteins called Toll-Like Receptors or TLRs. TLRs are critical in early immune response by sensing invading pathogens in the body, but in RA they end up targeting the joint itself.

In a previous study, blocking TLR signaling seemed to improve patients' symptoms. In the new study researchers also focused on TLRs but this time on the molecules that process signals from TLRs.

This molecule is called IRE1alpha. Mice without this molecule had reduced inflammation and were protected from developing rheumatoid arthritis. Normal mice treated with a drug that inhibits this molecule also did not get RA.

These results show TLR signaling may indeed play a key role in this disease. If scientists can replicate the results in humans, would they be protected from RA yet be more susceptible to infections? Much has yet to be worked out but if they could, the treatment would improve the lives of millions.