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Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption.

Yasmine Chabbi-Achengli1, Tereza Coman2, Corinne Collet3

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Serotonin plays a key role in rheumatoid arthritis. Lower serotonin levels in mice worsened arthritis, indicating serotonin

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Area of Science:

  • Immunology
  • Rheumatology
  • Neuroscience

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint destruction.
  • The role of serotonin in autoimmune diseases like RA is debated.
  • Serotonin's involvement in immune system activation and autoimmune reactions is unclear.

Purpose of the Study:

  • To investigate serotonin's role in collagen-induced arthritis (CIA) in mice.
  • To determine if reduced peripheral serotonin levels affect arthritis severity.

Main Methods:

  • Comparison of wild-type and Tph1(-/-) mice (with reduced serotonin) in a CIA model.
  • Assessment of clinical and pathological arthritis scores.
  • Analysis of paw inflammation, bone resorption, and immune cell populations (Th17, T-regulatory cells).
  • Evaluation of IL-17 levels and the effect of serotonin/agonists on immune cells ex vivo.

Main Results:

  • Wild-type mice showed increased paw serotonin with less inflammation during arthritis.
  • Tph1(-/-) mice exhibited exacerbated arthritis, increased osteoclast differentiation, and bone resorption.
  • Arthritic Tph1(-/-) mice had elevated IL-17 and Th17 cells, with reduced T-regulatory cells.
  • Ex vivo serotonin and 5-HT receptor agonists restored IL-17 secretion and Th17 differentiation in Tph1(-/-) mice.

Conclusions:

  • Serotonin is crucial in regulating the Th17/T-regulatory cell balance in arthritis.
  • Serotonin influences osteoclast differentiation and bone resorption in rheumatoid arthritis.
  • Targeting serotonin pathways may offer a novel therapeutic strategy for rheumatoid arthritis.