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T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients
Flora Reverchon1, Colleen Guillard2, Lucile Mollet2
1UMR7355, Experimental and Molecular Immunology and Neurogenetics, CNRS and University of Orléans, 45071 Orleans, France.
Biomedicines
|October 27, 2022
Summary
Serotonin's 5-HT7 receptor is upregulated in natalizumab-treated multiple sclerosis (MS) patients. Its activation promotes IL-10, suggesting a protective role in MS immunotherapy.
Area of Science:
- Neuroimmunology
- Immunology
- Pharmacology
Background:
- Serotonin (5-HT) modulates immune cells and is potentially protective in multiple sclerosis (MS) pathogenesis.
- The role and mechanisms of 5-HT receptors, particularly the 5-HT7 receptor, in MS remain largely unknown.
- The 5-HT7 receptor's ability to activate T cells and influence inflammation suggests potential involvement in MS.
Purpose of the Study:
- To investigate the expression of the 5-HT7 receptor on circulating lymphocytes in MS patients.
- To evaluate the impact of 5-HT7 receptor activation on cytokine production in peripheral blood mononuclear cells (PBMCs).
- To explore the potential role of the 5-HT7 receptor in the immunomodulatory effects of natalizumab in MS.
Main Methods:
- Collected blood samples from acute relapsing MS (ARMS) patients, natalizumab-treated (NTZ) MS patients, and control subjects.
- Investigated 5-HT7 receptor surface expression on T lymphocytes and CD4+ T cell subsets.
- Utilized peripheral blood mononuclear cell (PBMC) cultures and a selective 5-HT7 receptor agonist (5-carboxamidotryptamine, 5-CT) to assess cytokine production.
Main Results:
- A significant increase in 5-HT7 receptor surface expression was observed exclusively on T lymphocytes and CD4+ T cell subsets in NTZ-treated MS patients.
- Activation of the 5-HT7 receptor using 5-CT significantly promoted the production of interleukin-10 (IL-10) in PBMCs.
- This study is the first to report 5-HT7 receptor dysregulation in NTZ-MS patients and its association with increased IL-10 release.
Conclusions:
- The findings indicate a dysregulation of 5-HT7 receptor expression in natalizumab-treated MS patients.
- 5-HT7 receptor activation promotes IL-10 production, suggesting a potential immunosuppressive and protective role in MS.
- The 5-HT7 receptor may contribute to the immuno-protective mechanisms of natalizumab and represents a potential therapeutic target for MS.
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