T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients
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-HT&...
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MDPI AG
2022-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/10/2418 |
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| author | Flora Reverchon Colleen Guillard Lucile Mollet Pascal Auzou David Gosset Fahima Madouri Antoine Valéry Arnaud Menuet Canan Ozsancak Maud Pallix-Guyot Séverine Morisset-Lopez |
| author_facet | Flora Reverchon Colleen Guillard Lucile Mollet Pascal Auzou David Gosset Fahima Madouri Antoine Valéry Arnaud Menuet Canan Ozsancak Maud Pallix-Guyot Séverine Morisset-Lopez |
| author_sort | Flora Reverchon |
| collection | DOAJ |
| description | 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-HT<sub>7</sub> 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-HT<sub>7</sub> 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-HT<sub>7</sub> surface expression on T lymphocytes and on the different CD4<sup>+</sup> T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT<sub>7</sub>R 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-HT<sub>7</sub> expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT<sub>7</sub> 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. |
| first_indexed | 2024-03-09T20:38:53Z |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:38:53Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-68bf6b51562648c983b0ebc0d825ecc52023-11-23T23:02:43ZengMDPI AGBiomedicines2227-90592022-09-011010241810.3390/biomedicines10102418T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis PatientsFlora Reverchon0Colleen Guillard1Lucile Mollet2Pascal Auzou3David Gosset4Fahima Madouri5Antoine Valéry6Arnaud Menuet7Canan Ozsancak8Maud Pallix-Guyot9Séverine Morisset-Lopez10UMR7355, Experimental and Molecular Immunology and Neurogenetics, CNRS and University of Orléans, 45071 Orleans, FranceUPR4301, Center for Molecular Biophysics, CNRS, 45071 Orleans, FranceUPR4301, Center for Molecular Biophysics, CNRS, 45071 Orleans, FranceNeurology Department, Regional Hospital Orleans, 45100 Orleans, FranceUPR4301, Center for Molecular Biophysics, CNRS, 45071 Orleans, FranceUPR4301, Center for Molecular Biophysics, CNRS, 45071 Orleans, FranceMedical Information Department, Regional Hospital Orleans, 45100 Orleans, FranceUMR7355, Experimental and Molecular Immunology and Neurogenetics, CNRS and University of Orléans, 45071 Orleans, FranceNeurology Department, Regional Hospital Orleans, 45100 Orleans, FranceNeurology Department, Regional Hospital Orleans, 45100 Orleans, FranceUPR4301, Center for Molecular Biophysics, CNRS, 45071 Orleans, FranceSerotonin (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-HT<sub>7</sub> 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-HT<sub>7</sub> 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-HT<sub>7</sub> surface expression on T lymphocytes and on the different CD4<sup>+</sup> T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT<sub>7</sub>R 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-HT<sub>7</sub> expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT<sub>7</sub> 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.https://www.mdpi.com/2227-9059/10/10/2418serotonin5-HT<sub>7</sub> receptormultiple sclerosisnatalizumab treatmentT lymphocyte (T-cell)PBMCs (peripheral blood mononuclear cells) |
| spellingShingle | Flora Reverchon Colleen Guillard Lucile Mollet Pascal Auzou David Gosset Fahima Madouri Antoine Valéry Arnaud Menuet Canan Ozsancak Maud Pallix-Guyot Séverine Morisset-Lopez T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients Biomedicines serotonin 5-HT<sub>7</sub> receptor multiple sclerosis natalizumab treatment T lymphocyte (T-cell) PBMCs (peripheral blood mononuclear cells) |
| title | T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients |
| title_full | T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients |
| title_fullStr | T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients |
| title_full_unstemmed | T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients |
| title_short | T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients |
| title_sort | t lymphocyte serotonin 5 ht sub 7 sub receptor is dysregulated in natalizumab treated multiple sclerosis patients |
| topic | serotonin 5-HT<sub>7</sub> receptor multiple sclerosis natalizumab treatment T lymphocyte (T-cell) PBMCs (peripheral blood mononuclear cells) |
| url | https://www.mdpi.com/2227-9059/10/10/2418 |
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