Serotonin Deficiency Associated with Worse Rheumatoid Arthritis Symptoms

Rheumatoid arthritis (RA) was found to be worse in mice who were serotonin (5-hydroxytryptamine, 5-HT) deficient than in mice that were not, a recent study found.

“Our study highlights that 5-HT has a direct immunoregulatory role in arthritis,” said co-lead investigator Marie-Christine de Vernejoul. “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.”

The study published in The American Journal of Pathology consisted of a mouse model that experimentally induced RA, also known as collagen-induced arthritis, which is similar to human RA.

Researchers compared the effects of CIA in regular mice with genetically engineered mice with a tryptophan hydroxylase-1 deficiency, a key enzyme needed for serotonin production in peripheral tissues.

The results of the study showed that the number and activity of osteoclasts were found to be considerably higher in 5-HT deficient mice with arthritis. Furthermore, there was more bone resorption in the affected joints and remote sites.

Additionally, the 5-HT deficient mice with arthritis showed changes in cytokines in their paws (higher IL-17, higher TNF-α, and lower IL-4). There was a shift in the balance between T cell subtypes and Th17 lymphocytes.

“Altogether, our data show that 5-HT deficient mice are characterized by a relative, dampened expansion of Treg associated with an enhanced shift toward a Th17 phenotype, a situation previously described in patients with arthritis,” said co-lead investigator Francine Côté.

Later experiments that used cell cultures demonstrated that the balance between Th17/Treg cells were normalized when 5-HT or 5-HT receptor agonists were added. This showed that 5-HT played a direct role in RA.