Scientists from Japan has identified hidden immune 'hubs' that drive joint damage in patients with rheumatoid arthritis
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NEW DELHI — A team of scientists from Japan has identified hidden immune 'hubs' that drive joint damage in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease that affects millions worldwide and can have a devastating impact on patients' lives. Yet, about one in three patients responds poorly to existing treatments.
The team from Kyoto University discovered that peripheral helper T cells (Tph cells) -- a key type of immune cell involved in RA -- exist in two forms: stem-like Tph cells and effector Tph cells. The stem-like Tph cells reside in immune "hubs" called tertiary lymphoid structures within inflamed joints, where they multiply and activate B cells.
Some of these then become effector Tph cells that leave the hubs and cause inflammation. This continuous supply of effector Tph cells may explain why inflammation persists in some patients despite treatment.
Targeting the stem-like Tph cells at their source could offer a new therapeutic strategy, bringing hope for more effective symptom relief and improved quality of life for patients living with RA, the team explained in the paper, published online in the journal Science Immunology.
"Using cutting-edge analytical techniques that have only recently become available, we have uncovered a new aspect of the immune response at the sites of joint damage in RA," said first author Yuki Masuo from Kyoto.
"Because stem-like Tph cells can both self-renew and differentiate, they may represent a root cause of the disease."
Building on their earlier work, which showed that Tph cells build up in the joints of patients with RA and contribute to inflammation, the team analysed immune cells from inflamed joint tissue and blood of people with RA using a comprehensive approach called multi-omics. This combines different types of biological data to get a full picture of the dynamic behaviour of Tph cells in RA-affected joint tissue.
The results revealed that most stem-like Tph cells live inside these immune hubs, where they interact closely with B cells.
Further, by growing stem-like Tph cells and B cells together in the lab, the researchers found that this interaction not only helps stem-like Tph cells develop into effector Tph cells but also activates B cells.
On the other hand, effector Tph cells are found outside the hubs, where they interact with other immune cells, such as macrophages and cytotoxic (killer) T cells that promote inflammation.
Overall, the study reveals the presence of two types of Tph cells with different roles in inflamed joint tissue. Stem-like Tph cells live within immune hubs, where they self-renew and help activate B cells. Some of them mature into effector Tph cells, which then leave immune hubs and cause inflammation.