Cause of Rheumatoid Arthritis Discovered

Cause of Rheumatoid Arthritis Discovered

Little is known about the cause of rheumatoid arthritis, although new research has identified a specific cytokine that triggers and maintains inflammation.

Rheumatoid arthritis is a chronic inflammatory disease that involves inflammatory molecules called cytokines produced by the immune system. Inflammation is a non-specific response to pathogens that helps the body combat infection, although in the case of rheumatoid arthritis, the inflammatory response is not in response to a pathogen – the body turns on itself and causes chronic inflammation in the joints.

Certain inflammatory cytokines are known to play a role in maintaining inflammation – IL-6 and TNFα for example. Drugs have been developed that inhibit these cytokines, which have helped patients with rheumatoid arthritis to manage the condition. However, the treatments are not effective on all patients and new therapies are required.

While it has long been known that Th17 cells (white blood cells) are involved in autoimmune diseases such as rheumatoid arthritis, what was unclear is how they interact with and control other inflammatory cells at the site of inflammation. New research has cast some light on how Th17 influence cytokine production.

The international team of researchers, led by Japan’s Osaka University, used mouse models of rheumatoid arthritis to study how Th17 cells interacted with cells in the joint lining (synovium) that promote the degradation and destruction of cartilage and bone.

One inflammatory cytokine that plays an important role in the triggering of the condition is GM-CSF. The researchers discovered GM-CSF was essential for the development of arthritis in mice.

First author of the study, Keiji Hirota, explained that “GM-CSF produced both by stromal cells of the connective tissue and T cells contributed to joint inflammation in the mice, but only stromal cell-derived GM-CSF was needed to initiate arthritis.”

The researchers also showed that GM-CSF was secreted by stromal cells in response to stimulation by IL-17 from inflammatory Th17 cells. The team also discovered GM-CSF was secreted by a group of innate immune cells within inflamed joints, and those cells increased in number in response to the production of IL17 by Th17 cells, contributing to the maintenance of inflammation in mice.

“By selectively removing GM-CSF-producing cells from the mouse synovium, we significantly reduced the severity of arthritis,” said corresponding author Shimon Sakaguchi. “This suggests the usefulness of developing such a novel immunotherapeutic approach that targets the cellular network to reduce chronic joint inflammation.”

The research is detailed in the paper – Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis – which was recently published in the journal, Immunity.

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