Type -type peripheral T -shaped cells have proven to support inflammation in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that affects millions in the world. In addition, can have a devastating impact on patients’ lives. However, approximately one in three patients reacts badly to existing treatments. Furthermore, Researchers at the University of Kyoto have highlighted this challenge by discovering that peripheral Auxiliary T cells (TPH cells). Similarly, a key type of immune cells involved in PR, exist in two forms: TPH type TPH cells and effective TPH cells. In addition, TPH type TPH cells reside in immune “hubs” called tertiary lymphoid structures in the inflamed joints. Nevertheless, where they multiply and activate B cells. However, Some of them then become actuator cells that leave the hubs and cause inflammation. Nevertheless, This continuous diet of effective TPH cells can explain why inflammation persists in type -type peripheral t -shaped certain patients despite treatment. Nevertheless, The targeting of STEM type TPH cells at source could offer a new therapeutic strategy. Moreover, bringing hope for more effective relief of symptoms and a better quality of life for patients living with PR.

This research is led by Yuki Masuo. Nevertheless, a doctoral student at the Graduate School of Medicine from the University of Kyoto; Associate Professor Hiroyuki Yoshitomi of the Immunology Department (also an investigator associated with WPI-ASHBI), Graduate School of Medicine, University of Kyoto; And Professor Hideki Ueno, vice-director and principal researcher of WPI-Ashbi (also professor in the Department of Immunology, Graduate School of Medicine, Kyoto University, and director of the Kyoto University Immunological Monitoring Center, KIC). Nevertheless, These results will be published online in Scientific immunology August 15, 2025, at 2 p.m. local time (August 16 at 3:00 am JST).

Background – Type -type peripheral t -shaped

Rheumatoid arthritis (RA) is one of the most common type -type peripheral t -shaped autoimmune diseases, affecting around 18 million people worldwide. It occurs when the immune system mistakenly attacks the joints, resulting in chronic inflammation, pain, swelling and joint lesions. Although treatments have improved in recent years, about 30% of patients are still reacting to existing therapies. This underlines the need to better understand the underlying immune mechanisms of the disease in order to develop more. effective treatments for these patients.

Many types of immune cells are involved in the PR disease mechanism. Among them. the Auxiliary T cells act as the “commanders” of the immune system, recognizing threats and leading the activity of other immune cells. A recent study by the University of Kyoto revealed that a subset of Auxiliary TPH cells called TPH (TPH) peripheral cells accumulates in the joints of PR patients. contributes to inflammation. However. exactly where these TPH cells are located and activated in the joint and how type -type peripheral t -shaped they feed inflammation have not been fully understood.

Based on their previous work. the research team has analyzed immune cells of inflamed joint tissues and the blood of people with PR using a complete approach called multi-orders, which combines different types of biological data to obtain a complete image of the dynamic behavior of TPH cells in the joint tissue affected by the RA.

Key conclusions

Using the unique RNA sequencing. the team discovered two distinct types of TPH (TPH) of peripheral assistance in the fiery joint tissues: TPH type TPH cells, which can be self-renewed while retaining their identity, and the effective TPH cells, which are more activated but rarely divided. Over time, TPH type TPH cells can ripen in actuator TPH cells, but not the other way around.

The researchers then used a method called spatial transcriptomic to see exactly where the TPH cells are in the. inflamed type -type peripheral t -shaped joint. This method shows not only the location of TPH cells. but also the way they are arranged in relation to other immune and tissue cells (such as B cells, macrophages and fibroblasts) and immune “hubs” called tertiary lymphoid structures (TLSS). The results have revealed that most TPH type TPH cells live inside these immune centers. where they interact closely with B cells. By increasing STEM type TPH cells. together in laboratory B cells, researchers have noticed that this interaction not only helps TPH cells type STEM are transformed into TPH cells but also activate the B. On the side. effective TPH cells are located outside the concentrators, where they interact with other immune cells such as macrophages and cytotoxic (killer) T cells that promote inflammation.

Overall, this study revealed the presence of two types of TPH cells with different roles in the inflamed joint tissue. TPH type TPH cells type -type peripheral t -shaped live in TLSS, where they are renewed and help activate B cells. Some of them ripen in effective TPH cells, which then leave TLS and cause inflammation.

Perspectives futures

Using advanced analytical techniques that have only become recently available. we discovered a new aspect of the immune response to joint lesions in PR. Since TPH type TPH cells can both renew and differentiate themselves, they can represent a deep cause of the disease. “”

Yuki Masuo, first author

In PR patients who react poorly to treatment, the activity of TPH cells of STEM can help explain their persistent symptoms. Additional research on the functions of these cells could lead to new targeted therapies. potentially improving the relief of symptoms and improving the quality of life of these patients.