title: Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption.
abstract: Rheumatoid arthritis is a chronic disease that results in a disabling and painful condition as it progresses to destruction of the articular cartilage and ankylosis of the joints. Although the cause of the disease is still unknown, evidence argues that autoimmunity plays an important part. There are increasing but contradictory views regarding serotonin being associated with activation of immunoinflammatory pathways and the onset of autoimmune reactions. We studied serotonin's involvement during collagen-induced arthritis in wild-type and Tph1(-/-) mice, which have markedly reduced peripheral serotonin levels. In wild-type mice, induction of arthritis triggered a robust increase in serotonin content in the paws combined with less inflammation. In Tph1(-/-) mice with arthritis, a marked increase in the clinical and pathologic arthritis scores was noticed. Specifically, in Tph1(-/-) mice with arthritis, a significant increase in osteoclast differentiation and bone resorption was observed with an increase in IL-17 levels in the paws and in Th17 lymphocytes in the draining lymph nodes, whereas T-regulatory cells were dampened. Ex vivo serotonin and agonists of the 5-HT2A and 5-HT2B receptors restored IL-17 secretion from splenocytes and Th17 cell differentiation in Tph1(-/-) mice. These findings indicate that serotonin plays a fundamental role in arthritis through the regulation of the Th17/T-regulatory cell balance and osteoclastogenesis.
authors.affiliation: BIOSCAR, INSERM UMR_S1132, Hôpital Lariboisière, Unité Mixte de Recherche (UMR) 1132, Université Paris Diderot, Paris, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Chabbi-Achengli
authors.affiliation: Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Institut Imagine INSERM U1163/CNRS ERL 8254, Hôpital Necker, Paris, France.
authors.forename: Tereza
authors.initials: T
authors.lastname: Coman
authors.affiliation: BIOSCAR, INSERM UMR_S1132, Hôpital Lariboisière, Unité Mixte de Recherche (UMR) 1132, Université Paris Diderot, Paris, France; Department of Biology, Hôpital Lariboisière, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.affiliation: Department of Biology, Hôpital Lariboisière, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Callebert
authors.affiliation: BIOSCAR, INSERM UMR_S1132, Hôpital Lariboisière, Unité Mixte de Recherche (UMR) 1132, Université Paris Diderot, Paris, France.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Corcelli
authors.affiliation: BIOSCAR, INSERM UMR_S1132, Hôpital Lariboisière, Unité Mixte de Recherche (UMR) 1132, Université Paris Diderot, Paris, France.
authors.forename: Hilène
authors.initials: H
authors.lastname: Lin
authors.affiliation: INSERM UMR_S1151- CNRS UMR8253, Institut Necker Enfants Malades, Paris, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rignault
authors.affiliation: INSERM UMR_S1151- CNRS UMR8253, Institut Necker Enfants Malades, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.affiliation: BIOSCAR, INSERM UMR_S1132, Hôpital Lariboisière, Unité Mixte de Recherche (UMR) 1132, Université Paris Diderot, Paris, France. Electronic address: christine.devernejoul@aphp.fr.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: de Vernejoul
authors.affiliation: Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Institut Imagine INSERM U1163/CNRS ERL 8254, Hôpital Necker, Paris, France. Electronic address: francine.cote@parisdescartes.fr.
authors.forename: Francine
authors.initials: F
authors.lastname: Côté
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001862:Bone Resorption / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D018345:Mice, Knockout; D012701:Serotonin / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D012701:Serotonin