Analyses of peripheral blood dendritic cells and magnetic resonance spectroscopy support dysfunctional neuro-immune crosstalk in Tourette syndrome
Marianna Sarchioto
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy
Contribution: Data curation (lead), Formal analysis (lead), Investigation (lead), Project administration (lead), Validation (equal), Visualization (lead), Writing - original draft (lead), Writing - review & editing (equal)
Search for more papers by this authorFranklyn Howe
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (equal), Resources (equal), Supervision (supporting), Validation (supporting), Visualization (supporting), Writing - review & editing (supporting)
Search for more papers by this authorIngrid E. Dumitriu
Molecular and Clinical Sciences Research Institute, St George's, University of London and Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, London, UK
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (equal), Resources (equal), Supervision (supporting), Validation (supporting), Visualization (supporting), Writing - review & editing (supporting)
Search for more papers by this authorFrancesca Morgante
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Contribution: Project administration (supporting), Resources (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJeremy Stern
Atkinson Morley Regional Neuroscience Centre, St George's University of London, London, UK
Contribution: Resources (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMark J. Edwards
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Contribution: Conceptualization (supporting), Funding acquisition (equal), Project administration (supporting), Resources (equal), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Davide Martino
Department of Clinical Neurosciences, University of Calgary and Hotchkiss Brain Institute, Calgary, AB, Canada
Correspondence
Davide Martino, Department of Clinical Neurosciences, University of Calgary and Hotchkiss Brain Institute, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada.
Email: [email protected]
Contribution: Conceptualization (lead), Formal analysis (supporting), Funding acquisition (lead), Methodology (lead), Project administration (equal), Resources (equal), Supervision (lead), Validation (equal), Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (lead)
Search for more papers by this authorMarianna Sarchioto
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy
Contribution: Data curation (lead), Formal analysis (lead), Investigation (lead), Project administration (lead), Validation (equal), Visualization (lead), Writing - original draft (lead), Writing - review & editing (equal)
Search for more papers by this authorFranklyn Howe
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (equal), Resources (equal), Supervision (supporting), Validation (supporting), Visualization (supporting), Writing - review & editing (supporting)
Search for more papers by this authorIngrid E. Dumitriu
Molecular and Clinical Sciences Research Institute, St George's, University of London and Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, London, UK
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (equal), Resources (equal), Supervision (supporting), Validation (supporting), Visualization (supporting), Writing - review & editing (supporting)
Search for more papers by this authorFrancesca Morgante
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Contribution: Project administration (supporting), Resources (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJeremy Stern
Atkinson Morley Regional Neuroscience Centre, St George's University of London, London, UK
Contribution: Resources (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMark J. Edwards
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK
Contribution: Conceptualization (supporting), Funding acquisition (equal), Project administration (supporting), Resources (equal), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Davide Martino
Department of Clinical Neurosciences, University of Calgary and Hotchkiss Brain Institute, Calgary, AB, Canada
Correspondence
Davide Martino, Department of Clinical Neurosciences, University of Calgary and Hotchkiss Brain Institute, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada.
Email: [email protected]
Contribution: Conceptualization (lead), Formal analysis (supporting), Funding acquisition (lead), Methodology (lead), Project administration (equal), Resources (equal), Supervision (lead), Validation (equal), Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (lead)
Search for more papers by this authorFunding information
This work was supported by a research grant from Stiftung “Immunität und Seele”, Munich, Germany to Dr Davide Martino and Dr Mark J. Edwards.
Abstract
Background
Evidence supports that neurodevelopmental diseases, such as Tourette syndrome (TS), may involve dysfunctional neural-immune crosstalk. This could lead to altered brain maturation and differences in immune and stress responses. Dendritic cells (DCs) play a major role in immunity as professional antigen-presenting cells; changes in their frequency have been observed in several autoimmune conditions.
Methods
In 18 TS patients (15 on stable pharmacological treatment, three unmedicated) and 18 age-matched healthy volunteers (HVs), we explored circulating blood-derived DCs and their relationship with clinical variables and brain metabolites, measured via proton magnetic resonance spectroscopy (1H-MRS). DC subsets, including plasmacytoid and myeloid type 1 and 2 dendritic cells (MDC1, MDC2), were studied with flow cytometry. 1H-MRS was used to measure total choline, glutamate plus glutamine, total creatine (tCr), and total N-acetylaspartate and N-acetylaspartyl-glutamate levels in frontal white matter (FWM) and the putamen.
Results
We did not observe differences in absolute concentrations of DC subsets or brain inflammatory metabolites between patients and HVs. However, TS patients manifesting anxiety showed a significant increase in MDC1s compared to TS patients without anxiety (p = 0.01). We also found a strong negative correlation between MDC1 frequency and tCr in the FWM of patients with TS (p = 0.0015), but not of HVs.
Conclusion
Elevated frequencies of the MDC1 subset in TS patients manifesting anxiety may reflect a proinflammatory status, potentially facilitating altered neuro-immune crosstalk. Furthermore, the strong inverse correlation between brain tCr levels and MDC1 subset frequency in TS patients suggests a potential association between proinflammatory status and metabolic changes in sensitive brain regions.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author (D.M.), upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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