Hidden mechanism driving joint tissue growth in rheumatoid arthritis has been found

by Hospital for Special Surgery

edited by Stephanie Baum, reviewed by Andrew Zinin

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Researchers at Hospital for Special Surgery (HSS) have identified a specialized population of immune cells that plays a central role in driving abnormal tissue growth in rheumatoid arthritis (RA), offering new insight into disease progression and potential treatment strategies. The study, published in Science Translational Medicine, reveals that a subset of immune cells known as SPP1ʰⁱ macrophages works in tandem with structural cells and protein scaffolds to promote excessive tissue expansion in the joints of patients with RA.

RA is a chronic autoimmune disease that causes inflammation of the synovium—the tissue lining the joints—leading to pain, swelling and eventual damage to cartilage and bone. While current therapies largely focus on controlling inflammation, the mechanisms that drive the abnormal growth of synovial tissue—and its invasive portion, known as pannus, which erodes cartilage and bone—have remained poorly understood.

A new model of tissue growth in RA

Using advanced spatial transcriptomics to analyze human tissue samples, the HSS research team discovered that SPP1ʰⁱ macrophages cluster within fibrin-rich niches in the synovium. Fibrin, a protein typically involved in blood clotting and wound healing, appears to act as a temporary scaffold that supports new tissue formation.

Within these niches, the macrophages were found to:

• break down fibrin scaffolds through enzymatic activity and cellular uptake;
• stimulate nearby fibroblasts, key structural cells, to proliferate; and
• promote tissue remodeling and expansion independent of traditional inflammatory pathways.

"This work suggests that rheumatoid arthritis is not only driven by inflammation but also by dysregulated tissue repair processes," said Laura Donlin, Ph.D., senior author and scientist at the HSS Research Institute. "We are seeing a coordinated interaction between immune cells, structural cells and the extracellular matrix that fuels abnormal growth."

Beyond fibrosis: A distinct pathway

Interestingly, while SPP1ʰⁱ macrophages resemble cells involved in fibrotic diseases such as lung or liver fibrosis, the RA tissue environment lacks the dense collagen buildup characteristic of fibrosis. Instead, the researchers describe this process as "pro-generative" tissue remodeling, more closely resembling wound healing gone awry.

Therapeutic implications

The findings also suggest that targeting SPP1ʰⁱ macrophages and their signaling pathways could represent a new therapeutic approach. The study highlights the role of IL-6 signaling in sustaining these cells, offering further insight into why IL-6-targeting therapies, already used in RA, may be particularly effective in certain patient populations.

"Current treatments focus on suppressing inflammation, but our findings point to additional pathways that drive disease progression," said Donlin. "Targeting these tissue remodeling processes could open the door to more precise and effective therapies."

The study's findings may extend beyond RA. Similar immune cell populations and fibrin-based remodeling processes have been implicated in other conditions, including interstitial lung disease, lupus, cancer and traumatic injury, suggesting a broader role for this pathway in human disease.

Publication details

Ian Mantel et al, SPP1hi macrophages in fibrin niches promote hyperplastic tissue remodeling in rheumatoid arthritis synovium, Science Translational Medicine (2026). DOI: 10.1126/scitranslmed.aed3087

Journal information: Science Translational Medicine

Key medical concepts

Rheumatoid ArthritisSpatial TranscriptomicsFibrin

Clinical categories

RheumatologyAllergy and immunology Provided by Hospital for Special Surgery Who's behind this story?

Stephanie Baum

Master's in TESOL from The New School. Passionate about language learning and editing science news on biology and space exploration. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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