The average person likely doesn’t know if TLR5 is an airplane model, a Twitter handle, or a license plate number. As it turns out, TLR5 may be part of the solution to the complex puzzle that is rheumatoid arthritis (RA).
TLR5, or “toll-like receptor 5,” is a protein that is encoded by the TLR5 gene. The TLR family of genes is responsible for our innate immunity. Rheumatoid arthritis is an autoimmune disease, meaning that the body’s immune system produces a faulty response that causes immune system cells to attack healthy joints, organs, and tissues.
How Is TLR5 Linked to RA?
Researchers have found that targeting the TLR5 protein may have a positive effect when it comes to fighting RA. TLR5 is specifically found on myeloid cells, which are a component of bone marrow. These cells in particular migrate through the bloodstream and eventually into the joints. If these cells can be targeted and halted, inflammation in the joints and other organs may eventually be stopped, too.
You might think it could be dangerous to destroy myeloid cells and TLR5, but researchers have found that rheumatoid arthritis patients actually have an abundance of TLR5 on their myeloid cells — far more than their healthy counterparts do. This may contribute, at least in part, to disease activity in RA patients.
In fact, a study published this month in the Journal of Immunology showed that TLR5 can actually trigger the RA disease processes.
TLR5 and TNF-alpha Team Up to Destroy Joints
Researchers have also found a link between TLR5 and TNF-alpha pathways. Rheumatoid arthritis patients may be familiar with the term TNF-alpha, considering that anti-TNF drugs are among the most common biologic drugs on the market to treat RA. Anti-TNF drugs target an inflammation-causing substance in the body called TNF, or tumor necrosis factor.
The new study shows that when the joint fluid of an RA patient contains this activated TLR5, it in turn also increases levels of TNF-alpha. The reverse is also true, so the anti-TNF drugs that many RA patients take may reduce TLR5, as well.
Shiva Shahrara, Ph.D., who led the study and is an associate professor of rheumatology at the University of Illinois at Chicago, explained her hypothesis.
“Basically what it means is that TLR5 and TNF work together in attracting or recruiting specific cells from the blood into the RA joint, which contributes to joint inflammation,” she said. “TLR5 and TNF also work together in transforming the cells recruited from the blood circulation into bone-eroding osteoclasts.” These bone-eroding osteoclasts contribute to bone loss.
So, when an overabundance of TLR5 meets TNF-alpha, it spells disaster for joints. These two “bad guys” work together to create inflammation and contribute to disease activity in RA.
Finding out how to isolate and deactivate the TLR5 protein may help stop this vicious cycle of inflammation and disability. According to Shahrara’s research team, TLR5 is a promising new target for RA treatment.