The found immune molecule plays a key role in the regulation of inflammation in rheumatoid arthritis

Scientists from the University of Kyoto found that the immune molecule appearing only in the primary, called IGFL2, plays a key role in the regulation of inflammation in rheumatoid arthritis (RA). IGFL2 is produced by a subset of immune cells in patients with RA and acts as fuel on fire: it activates more immune cells, additionally strengthening inflammation and deterioration of joint damage. They also discovered that IGFL2 levels were much higher in the blood of patients with RA, especially in people with severe symptoms. These discoveries confirm the potential of IGFL2 as a diagnostic marker, a tool for monitoring the disease progression and the purpose of new therapies, paving the way to prior detection, more effective treatment and better quality of life of people from RA around the world.

Review

Rheumatoid arthritis (RA) is chronic autoimmune disease in which the immune system incorrectly attacks the lining of the joints (Mazia), causing pain, swelling and progressive damage. About 18 million people around the world live from Ra. Early diagnosis and treatment can alleviate symptoms, slow progression of the disease and help prevent disability. Current therapies focus on reducing inflammation and maintaining joint function, but up to 30% of patients do not react well. This emphasizes the urgent need to better understand his pathology of early diagnosis and the development of more effective therapies.

Helper Cells T. They are a kind of white blood cells that act as a “commanders” of the immune system. They play a key role, recognizing threats and coordinating immune answers. However, in autoimmune diseases, such as RA, these commanders become disturbed and cause that the immune system attacks their own tissues of the body. Although it is known that Auxiliary T cells are the main players in RA, precise molecular mechanisms that drive inflammation are still unclear. Now scientists from the University of Kyoto have discovered a cytokine specific to primates called IGFL2, produced by a subset with auxiliary cells known as the cells of the T (TPH) assistant in the ponds of patients with RA. Their findings suggest that IGFL2 helps regulate inflammation in the synovial tissue of affected joints and can serve both as a marker of disease activity and the promising goal of new therapies.

The research is conducted by the Akinori Murakami assistant professor from the Institute of Advanced Biology Study Human (WPI-ASHBI), Kyoto University; Extraordinary professor Hiroyuki Yoshitomi from the Immunology Department (also a researcher of a collaborator at WPI-ASHBI), Graduate School of Medicine; Professor Hideki Ueno, vice director and main researcher at WPI-ASHBI (also a professor at the Faculty of Immunology, Graduate School of Medicine and director of Kyoto University Immunological Monitoring Center, KIC); and Professor Shuichi Matsuda from the Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University. The discoveries will be published on August 1, 2025.

Key arrangements

Using the data of gene expression from unicellular analysis and clinical information, scientists analyzed individual auxiliary T cells from the common tissue of patients with RA. They identified a separate subgroup known as TPH cells, which are closely related to a more severe disease. In particular, these cells produce IGFL2 (insulin growth factor similar to growth factor 2), cytokine only found in primates. IGFL2 was expressed only in auxiliary T cells in synovial tissue, with the highest levels observed in TPH cells.

Then scientists examined how IGFL2 drives inflammation in RA. They discovered that IGFL2 increases protein production called CXCL13, which promotes the production of autoantibodies. In addition, IGFL2 activates immune cells known as monocytes and macrophages, additionally strengthening inflammation and damage to the joints. This is confirmed by the fact that IGFL2 blocking reduces the activation of these cells.

To assess its clinical significance, the team measured IGFL2 levels in blood samples from patients with RA. IGFL2 levels were much higher in patients compared to healthy people, and even higher in patients with more severe symptoms. His ability to distinguish patients with healthy people was similar to commonly used diagnostic markers.

To sum up, these discoveries suggest that IGFL2 is not only a marker of disease activity, but can also actively drive inflammation in RA, which makes him a promising goal of new treatment methods.

Future prospects

– said Hiroyuki Yoshitomi, the main author of the article.

Going further, scientists strive to explain how IGFL2 expression and its functions in the immune system are regulated. This work will deepen the understanding of RA pathology and can lead to more precise diagnostics, innovative targeted therapies, and ultimately better results and quality of life of people affected by RA and other autoimmune diseases.

Glossary

• Auxiliary cells T: A type of white blood cells that acts as a “commander” of the immune system. They play a key role in managing the immune response, helping B cells producing antibodies and supporting the activation of other immune cells in response to foreign infections or substances.
• Single -cell analysis: A technique that insulates RNA from individual cells and analyzes, which genes are expressed and to what extent at a single -cell level. Unlike traditional mass analysis, which provides only average data from the cell group, one -cell analysis allows scientists to observe the differences between individual cells, identify rare types of cells and trace processes, such as activation of immune cells and cell differentia.
• Peripheral TPH T cells (TPH cells): Auxiliary T subbaration in inflammatory tissues and helps in creating structures to maintain immunological activation.
• Cytokine: Small protein released by cells that affects the behavior of other cells, especially in immune response.
• Monocytes/macrophages: Immune cells involved in detecting, absorbing and destroying pathogens and cell residues. Monocytes circulate in the blood and migrate to tissues, where they differentiate in macrophages.