In the colon, knocking out IL-10 in the FOXP3 population gives rise to severe inflammation in mice.
It also appears to be just as important in humans. Researchers at Erasmus found that a girl with severe enterocolitis had a mutation within the IL-10 receptor alpha gene. Within samples of her dendritic cells, tumor necrosis factor and IL-6 were not downregulated as in the healthy control cells.
It was also found that IL-10 drastically reduces interferon gamma and IL-17 in the healthy cells, but not in the patient’s cells.
“IL-10 signaling is critical to maintain tolerance…in the human colon,” Dr. Samsom said. She said this could help lead to new insights into the control of TH1 and TH17 cells, which could lead to better-tailored treatments.
A Bigger Role for Bacteria?
John Carter, MD, associate professor and chief of the rheumatology division at the University of South Florida in Tampa, said evidence is emerging that bacteria’s role in reactive arthritis—and even undifferentiated spondylarthropathy in general—might be bigger than researchers have thought.
“One [type of] bacteria can cause a classic triad of symptoms in a certain patient and incomplete or a complete absence of this classic triad of symptoms in another,” he said. “Some patients will have spontaneous remission, some patients will develop chronic disease, all from the same bacteria. So, clearly this is a little more complex than originally thought.”
Ocular serovars might play a big part in Chlamydia-based reactive arthritis, he said. It’s been the prevailing view that the genital serovars were the cause of reactive arthritis because the infection is passed genitally but, “it’s important to remember that very rarely you can actually pass the ocular serovars genitally.”
Researchers at Wayne State University and the University of South Florida analyzed serovars of 36 patients with polymerase chain reaction–confirmed synovial Chlamydia trachomatis and found that they were all ocular serovars, with no genital serovars.1
Dr. Carter noted that there are genetic differences between ocular and genital serovars that might explain ocular serovars’ role in causing arthritis.
“If you think about the clinical symptoms of reactive arthritis, often times you have eye involvement, so perhaps this goes a long way in explaining some of the clinical features,” Dr. Carter said.
These recent discoveries “challenge the notion that these bacteria simply trigger an autoimmune response and do not play a role in disease maintenance,” he says. “And it suggests that perhaps too much emphasis has been placed on the host in terms of disease genesis and maintenance” in post-Chlamydial reactive arthritis.