Purinergic Profiling of Regulatory T-cells in Patients With Episodic Migraine.

Dilyara Nurkhametova,Rashid Altunbaev,Olga Khayrutdinova,Igor Kudryavtsev,Rashid Giniatullin,Tarja Malm,Maria Serebryakova

doi:10.3389/fncel.2018.00326

Abstract

Objectives: Immune responses in migraine are poorly characterized, yet implicated in the disease pathogenesis. This study was carried out to characterize purinergic profiles of T-cells in patients with episodic migraine without aura (MWoA) to provide mechanistic evidence for ATP and adenosine involvement in modulation of immune regulation in migraine.Methods: Peripheral blood samples were obtained from patients with migraine (n = 16) and age-matched control subjects (n = 21). Subsets of T-cells were identified by flow cytometry based on specific membrane markers.Results: Migraine patients showed reduced total T-cell counts in the peripheral blood. Whereas the total number of CD3+CD4+, CD3+CD8+, or regulatory T lymphocytes (Treg) was not changed, the proportion of Treg CD45R0+CD62L– and CD45R0–CD62L– cells was increased. Interestingly, in migraine, less Treg cells expressed CD39 and CD73 suggesting disrupted ATP breakdown to adenosine. The negative correlations were observed between the duration of migraine and the relative number of CD73+CD39– Tregs and total number of CD73-positive CD45R0+CD62L+ Tregs.Conclusion: Obtained data indicate that T-cell populations are altered in episodic migraine and suggest the involvement of Tregs in the pathophysiology of this disorder. Reduced expression of CD39 and CD73 suggests promotion of ATP-dependent pro-inflammatory and reduction of adenosine-mediated anti-inflammatory mechanisms in migraine.

Highlights

Migraine is a very common neurological disorder in the modern population
We demonstrate that the Treg expression of CD39 and CD73 is reduced suggesting promotion of purinergic mechanisms of inflammation
Our data revealed that the total CD3+ T cell population was slightly decreased in migraine patients compared to healthy controls (p = 0.021, Table 2)

Summary

Introduction

Migraine is a very common neurological disorder in the modern population. There are two main types of migraine: migraine with aura (MWA) and migraine without aura (MWoA). Nociceptive trigeminal nerves in dura mater, a likely source of migraine pain (Moskowitz and Cutrer, 1993; Bolay et al, 2002; Olesen et al, 2009; Zakharov et al, 2015), are surrounded by mast cells (Levy, 2009; Kilinc et al, 2017) and T-cells, apparently associated with recently discovered meningeal lymphatic vessels (Aspelund et al, 2015; Louveau et al, 2015). The levels of SuPAR have been reported to be elevated during migraine attack compared to healthy individuals and patients with migraine in the interictal period (Yılmaz et al, 2017)

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