A team of researchers led by The Ohio State University has unveiled a crucial link between gut bacteria and the systemic impacts of rheumatoid arthritis. This discovery could pave the way for innovative treatments for autoimmune diseases.
In a new study, researchers led by The Ohio State University College of Medicine have discovered a pivotal connection between “good” gut bacteria and the onset of rheumatoid arthritis, a chronic autoimmune disease. This finding offers a new perspective on how gut health can influence systemic autoimmune conditions.
Over the years, the research team meticulously traced the origin and migration pattern of an unusual type of immune cell in mice.
In this new study, they revealed how commensal bacteria, which are typically beneficial, can trigger the production and release of a type of T cell originating from the gut, leading to widespread autoimmune disease.
“This is really the first time it’s been shown that T cell plasticity, which typically occurs in the gut, can have this dramatic impact outside the gut with systemic impact on autoimmune disease,” senior author Hsin-Jung Joyce Wu, a professor of internal medicine in the division of rheumatology and immunology at The Ohio State University College of Medicine, said in a news release.
Published in Nature Immunology, the research underscores that many gene expressions found in the abnormal cells in mice also exist in the same cells in humans with rheumatoid arthritis (RA). This correlation suggests that the findings could be relevant to human patients.
Rheumatoid arthritis affects approximately 18 million people worldwide and is characterized by chronic inflammation and joint pain. Although the exact cause remains elusive, factors such as genetics, smoking and changes in gut bacteria (dysbiosis) are known to elevate risk.
The study centers around an abnormal T cell identified as T follicular helper 17 (TFH17) cells, which exhibit a hybrid nature, combining attributes of TFH cells and T helper 17 (TH17) cells. These cells, unlike conventional TFH cells that stay localized in B cell follicles, have the mobility trait of TH17 cells, allowing them to migrate to infection sites and produce the inflammatory protein IL-17.
Why It Matters
Traditionally, TFHcells are assumed to be stationary, residing within B cell follicles to aid in immune responses. The discovery that TFH17 cells also possess the mobility of TH17 cells indicates a novel mechanism by which gut bacteria influence systemic autoimmune diseases.
“That’s what makes them ultra-pathogenic TFH cells in RA, a systemic disease, because they are very mobile and can potently help B cells,” Wu added.
To pinpoint the cells’ origins, the team utilized advanced mouse models and fluorescent tagging techniques. They found that these TFH17 cells were induced by typically harmless segmented filamentous bacteria in lymphoid tissue within the small intestine, known as Peyer’s patches.
The implications extend beyond rheumatoid arthritis. Given that similar TFH17 cells have been detected in lupus patients, this research could pave the way for broader applications in treating various autoimmune diseases.
“For the future, as TFH17 cells can be found in other type of autoimmune patients, such as lupus patients, if we can determine that these abnormal TFH cells are a potential target not just for RA, but across autoimmune diseases, that would be very useful,” added Wu.
Support and Collaboration
This research was funded by the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute, with contributions from experts across institutions, including Weill Cornell Medicine, the University of Arizona, the University of Utah, the National Center of Gerontology in Beijing and Harvard Medical School.
Source: The Ohio State University