Researchers have shown for the first time that serotonin plays a fundamental role in the pathology of rheumatoid arthritis, through the regulation of essential regulatory immune cells and cells responsible for bone re-absorption. The findings might constitute a new treatment approach for rheumatoid arthritis.
The research paper, “Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption,” was published in The American Journal of Pathology.
Rheumatoid arthritis (RA) is a chronic painful disease characterized by abnormal inflammation, stiffness, and swelling of the joints, leading to limited motion and function. Although the definite cause of rheumatoid arthritis is still unknown, growing evidence shows a crucial involvement of autoimmunity. Serotonin (5-hydroxytryptamine, or 5-HT), a neurotransmitter, has been studied due its possible involvement in the onset of autoimmune reactions, although evidence has remained contradictory.
Researchers investigated serotonin involvement in RA pathology in mouse models of the disease. Analyzing two groups of animals, one with normal serotonin function (wild-type) and another with marked low peripheral levels of the neurotransmitter, the team observed that in the wild-type group induction of rheumatoid arthritis elicited a strong increase in serotonin content in their paws. But mice modified to not produce serotonin showed a marked increase in clinical and pathologic arthritis scores, osteoclast differentiation, and bone resorption.
Researchers also observed that serotonin-deficient mice with arthritis displayed a shift in the balance of immune cells, primarily regulatory T-cells and Th17 lymphocytes. This shift toward a Th17 phenotype has also been observed in RA patients. Importantly, researchers found that disease characteristics were reduced by treatment with serotonin or compounds that activate serotonin receptors, revealing a direct regulatory role of serotonin in rheumatoid arthritis.
“Our study highlights that 5-HT has a direct immunoregulatory role in arthritis,” co-lead investigator Marie-Christine de Vernejoul said in a press release. “The development of treatments targeting 5-HT or 5-HT receptors could represent an exciting prospect to regulate the immune response in RA and open new perspectives to improve the therapeutic options for patients.”
