Objective: We aimed to study in vivo aspects of neuro-inflammation in Tourette syndrome (TS) patients exploring frequency and distribution of circulating blood-derived dendritic cells and their relationships with clinical parameters and brain metabolites.

Background: Evidence supports that TS, like other neurodevelopmental diseases, may involve dysfunctional neuro-immune cross-talk, ultimately leading to altered brain maturation  pathways controlling different behavioural domains and, possibly, differences in immune-related stress responses¹

Method: We studied 18 patients and 18 healthy controls (HC). Subjects with inflammatory and auto-immune diseases, or recent corticosteroid treatments were excluded. Demographic data and measures of disease severity were collected including Adult ADHD scale, Yale Global Tic Severity Score, Yale-Brown Obsessive Compulsive Scale, and Beck Anxiety and Depression score. Blood dendritic cells (DC), plasmacytoid (pDC) and myeloid type 1 and 2(mDC1, mDC2) were studied with flow cytometry. MRI spectroscopy was acquired in frontal white matter (FWM) and putamen (PUT) to measure total choline (tCho), myo-inositol, total creatines (tCr), N-acetyl aspartate and Glutathione (GSH).

Results: Groups were similar for demographic and clinical characteristics. There were no differences in absolute concentrations of DC subsets or brain imetabolites between patients and HC. There was a positive correlation between PUT GSH levels and ADHD, anxiety and depression in the TS cohort. TS patients with anxiety (TS-A) showed significant increase of mDC1 compared to TS patients without anxiety (TS-NA) (p=0.03). TS-A showed reduction of GSH and GSH/Cr ratio in PUT compared to TS-NA and HC (p=0.04, p=0.03). TS-NA showed a reduction of PCho compared to HC (p=0.02). Finally, there was a strong inverse correlation between mDC1 and tCr in FWM in TS patients (p=0.004).

Conclusion: Our data indicate an increased frequency of mDC1 in anxious TS patients, likely related to stress response. Current literature suggests that endogenous cortisol release may increase circulating DC precursors² and impair maturation³ and antigen presentation⁴. Moreover, changes in GSH and PCho brain levels have been respectively linked to oxidative stress in anxiety⁵ disorders and neuroinflammation⁶. Finally, the strong correlation between DC and brain metabolites, may support the hypothesis of a relationship between innate immune cell dysfunction and metabolic brain changes in TS patients.

References: 1) Martino D et al. The role of immune mechanisms in Tourette syndrome. Brain Res 2015; 1617:126-143 2) Hunzeker JT at al. A Marked Reduction in Priming of Cytotoxic CD8+ T Cells Mediated by Stress-Induced Glucocorticoids Involves Multiple Deficiencies in Cross-Presentation by Dendritic Cells. J Immunol January, 186 (1) 183-194 3) Elftman et al. Corticosterone impairs dendritic cell maturation and function. Immunology 2007, 122: 279-290. 4) M.E. Truckenmiller et al. Stress presents a problem for dendritic cells: Corticosterone and the fate of MHC class I antigen processing and presentation. Brain Behav Immun. 2006 May;20(3):210-8 5) Hassan W et al. Association of oxidative stress to the genesis of anxiety: implications for possible therapeutic interventions. Curr Neuropharmacol. 2014;12(2):120–139. 6) Qin, J. et al. Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. J. Neurosci. 2007 Res., 85: 977-984

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dendritic-cells-and-brain-metabolites-in-tourettes/