T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients - Archive ouverte HAL
Article Dans Une Revue Biomedicines Année : 2022

T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients

Flora Reverchon
  • Fonction : Auteur
Immunologie et Neurogénétique Expérimentales et Moléculaires
Colleen Guillard
  • Fonction : Auteur
Lucile Mollet
  • Fonction : Auteur
Pascal Auzou
  • Fonction : Auteur
David Gosset
Fahima Madouri
  • Fonction : Auteur
Antoine Valéry
Arnaud Menuet
  • Fonction : Auteur
Canan Ozsancak
Maud Pallix-Guyot
  • Fonction : Auteur
Séverine Morisset-Lopez
CV

Résumé

Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT7 receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood sample from three groups: acute relapsing MS patients (ARMS), natalizumab-treated MS patients (NTZ), and control subjects. We investigated the 5-HT7 expression on circulating lymphocytes and evaluated the effects of its activation on cytokine production with peripheral blood mononuclear cell (PBMC) cultures. We found a significant increase in the 5-HT7 surface expression on T lymphocytes and on the different CD4+ T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT7R activation significantly promotes the production of IL-10, a potent immunosuppressive cytokine in PBMCs. This study provides for the first time a dysregulation of 5-HT7 expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT7 may play a role in the immuno-protective mechanisms of NTZ in MS disease and could be considered as an interesting therapeutic target in MS.

Domaines

Biologie cellulaire Immunologie

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https://hal.science/hal-03806213

Soumis le : vendredi 7 octobre 2022-16:00:30

Dernière modification le : vendredi 3 mai 2024-17:06:15

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Dates et versions

hal-03806213 , version 1 (07-10-2022)

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Flora Reverchon, Colleen Guillard, Lucile Mollet, Pascal Auzou, David Gosset, et al.. T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients. Biomedicines, 2022, 10 (10), pp.2418. ⟨10.3390/biomedicines10102418⟩. ⟨hal-03806213⟩

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