Researchers from Keio University School of Medicine in Japan have identified a previously unknown immune mechanism that may be responsible for sustaining the chronic autoimmune response seen in Sjögren’s disease. The discovery sheds new light on how the disease progresses and could open the door to targeted treatments that avoid the broad immune suppression associated with current therapies.
The findings, published in Science Advances on June 3, 2026, reveal a self-perpetuating interaction between CD4+ T cells and B cells that continuously fuels autoimmune activity in patients with Sjögren’s disease.
Sjögren’s disease affects millions of people worldwide and is characterized by the immune system mistakenly attacking moisture-producing glands, particularly the salivary and tear glands. Patients commonly experience chronic dry mouth and dry eyes, but the disease can also damage organs such as the lungs, kidneys, skin, and nervous system.
Although several treatments can help manage symptoms, there is currently no cure. Most available therapies rely on immunosuppressive drugs that broadly dampen immune activity, leaving patients more vulnerable to infections and other complications.
One of the defining features of Sjögren’s disease is the production of anti-Ro60 autoantibodies, which mistakenly target the body's own Ro60 protein. While researchers have long recognized the role of antibody-producing B cells, the contribution of CD4+ T cells has remained less clear.
To better understand this relationship, Assistant Professor **Masaru Takeshita** and colleagues analyzed immune cells collected from the salivary glands of patients with Sjögren’s disease. Using advanced single-cell RNA sequencing and T-cell receptor (TCR) analysis, the team examined hundreds of immune cell receptors involved in recognizing disease-related targets.
Their investigation led to the identification of disease-associated CD4+ T cells that specifically recognize fragments of the same Ro60 protein targeted by autoantibodies. This marks the first direct evidence that both major immune cell populations involved in the disease are responding to a common antigen.
Further experiments uncovered a mechanism that helps explain why the disease becomes chronic. The researchers found that anti-Ro60 antibodies bind to Ro60 proteins released from damaged cells, forming immune complexes. These complexes are readily captured by antigen-presenting cells, which process and display Ro60 fragments to CD4+ T cells.
Once activated, these T cells stimulate B cells to produce even more anti-Ro60 antibodies, creating a continuous cycle of immune activation and tissue damage.
According to the research team, this self-reinforcing loop may be one of the central drivers of persistent inflammation in Sjögren’s disease. Importantly, the mechanism was observed in both Japanese and Caucasian patients, suggesting that the newly identified pathway is not restricted to a specific ethnic or genetic background. This broad consistency increases confidence that the findings represent a fundamental feature of anti-Ro60-positive Sjögren’s disease and may be relevant to a large proportion of patients worldwide.
The discovery could have significant therapeutic implications. Current treatments suppress large portions of the immune system, often affecting beneficial immune responses alongside harmful ones. By specifically targeting the newly identified interaction between Ro60-reactive T cells and B cells, researchers believe it may be possible to interrupt disease progression without compromising overall immune protection.
Such an approach could reduce the risk of infections and other side effects commonly associated with long-term immunosuppressive therapy.
The Keio University team plans to further investigate how this immune feedback loop can be disrupted therapeutically. Researchers also hope the findings will provide insights into other autoimmune diseases that involve similar interactions between T cells, B cells, and autoantibodies.
As scientists continue to unravel the complex immune mechanisms behind Sjögren’s disease, this discovery represents a major step toward developing safer, more targeted treatments that address the root causes of autoimmunity rather than simply controlling symptoms.
