When the debilitating effects of rheumatoid arthritis (RA) come on, it tends to happen in the same joints that have previously been stiff, swollen, or in pain before – and that remains the case even if there's a long time between each flare-up. According to new research conducted on mice, this could be because our immune system keeps a record of these past afflictions, creating a personalized disease pattern in each individual. Understanding more about how and why this happens could open up new opportunities for treating the disorder. This latest study zooms in on the T cells in mice's bodies, white blood cells that are key to the immune system. In particular, the T cells in the synovium – the tissue lining the inside of the capsule around each joint – appear to hold a memory of previous RA problems. "Overwhelmingly, flares occur in a previously involved joint," says immunologist Peter Nigrovic from Boston Children's Hospital. "Something in that joint seems to remember, 'this is the joint that flared before'." "We showed that these T cells anchor themselves in the joints and stick around indefinitely after the flare is over, waiting for another trigger. If you delete these cells, arthritis flares stop." This was demonstrated through two mouse models using chemical triggers to cause joint inflammation and one mouse model using a genetic trigger to generate the same effect: The researchers removed a protein that blocked the pro-inflammatory cytokine IL-1. These triggers caused T cells to rally other cells to the immunity cause, leading to arthritis flare-ups in specific joints in the mice. When these T cells were taken out, additional inflammation was prevented. These T cells don't move between joints and take up "long-term residency" where they are, the researchers say, ready to be reactivated again. The approach taken here was actually inspired by skin studies. T cells with a form of memory are known to reside in the skin, leading to repeating patterns in skin problems such as psoriasis. It also happens with reactions to nickel in jewelry or wristwatches. "A person reacting to nickel through a belt buckle may also develop a rash on their wrist, where they wore a nickel-containing watch as a child," says Nigrovic. The team thinks that other types of autoimmune arthritis could work in the same way, which could lead to better treatments and approaches to these issues. The next step is to confirm that the same process happens in humans and find out ways to target it. It's possible that other mechanisms are also playing a part in this RA memory retention, the researchers say – it could be that T cells are the main cause in some cases but not others. That's something that further studies in the future should be able to analyze. With millions of people affected by rheumatoid arthritis across the world, any kind of alleviation of pain or management of symptoms is going to be welcome. The good news is that scientists are constantly discovering more about how the disorder operates. "Right now, treatment of rheumatoid arthritis has to continue lifelong," says Nigrovic. "Although we can successfully suppress disease activity in many patients, there is no cure. We think our findings may open up new therapeutic avenues." Source
