New Immune 'Centers' Discovered in Rheumatoid Arthritis Joints

Rheumatoid arthritis (RA) is a global autoimmune disease that affects millions and can dramatically impact patients' lives. However, approximately one-third of patients do not respond well to current treatments.

The Kyoto University research team has revealed new insights into this issue by identifying two forms of peripheral helper T cells (Tph cells), which play a crucial role in RA: stem-like Tph cells and effector Tph cells. The stem-like Tph cells are located in immune "centers" known as tertiary lymphoid structures within swollen joints, where they multiply and activate B cells.

Some of these become effector Tph cells that exit the centers to cause inflammation. This continuous cycle of generating effector Tph cells may explain why some patients experience persistent inflammation despite treatment.

Targeting stem-like Tph cells at their source could offer a new therapeutic option, potentially leading to more effective symptom relief and improved quality of life for RA sufferers.

The findings have been published in Science Immunology.

The research team includes Yuki Masuo, a doctoral student at Kyoto University's Graduate School of Medicine; Associate Professor Hiroyuki Yoshitomi from the Department of Immunology (also an associate investigator with WPI-ASHBi); and Professor Hideki Ueno, who is Vice Director and Principal Investigator for WPI-ASHBi.

RA results from the immune system attacking joints, leading to chronic inflammation, pain, swelling, and joint damage. Although treatments have improved over time, about 30% of patients respond poorly to current therapies. This highlights the need to better understand RA's underlying immune mechanisms to create more effective treatments.

The immune response in RA involves many cell types, with helper T cells acting as "commander" cells by recognizing threats and directing other immune cells' activity.

A recent study from Kyoto University found that a subset of helper T cells called peripheral helper T (Tph) cells accumulates in RA patients' joints, contributing to inflammation. However, the exact locations where these Tph cells are activated within the joint and how they fuel inflammatory responses were not wholly understood until now.