Regulatory T cells participate in the recovery of ischemic stroke patients

Abstract

Background: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. Methods: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. Results: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = − 0.414) and 72 h (r = − 0.418) and infarct volume. Conclusions: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

TREGking From Gut to Brain: The Control of Regulatory T Cells Along the Gut-Brain Axis

“…Co-culturing astrocytes with splenic T cells showed that astrocytes help to sustain FOXP3 expression in Tregs through IL-2/STAT5 signaling ( 114 ). Recently, a study reported higher circulating Tregs and serum IL-10 level at 48 and 72 hours after stroke onset in patients ( 115 ). To further identify the association of Tregs frequency with clinical outcomes, stroke patients are divided into two groups based on disease outcome (good vs. poor based on modified Rankin scale) and found the poor clinical outcomes with a higher infection risk especially in patients with lower Tregs frequency at 48 hours after stroke ( 115 ).…”

Clinical perspectives on the age-related increase of immunosuppressive activity

“…Studies conducted on cardiovascular diseases, e.g., atherosclerosis, hypertension, acute coronary syndrome, and stroke, have indicated that immunosuppressive cells were involved in the pathology of CVD [ 116 – 119 ]. For instance, the occurrence of a stroke increased the level of Tregs which attenuated inflammatory responses and enhanced the appearance of post-stroke regeneration [ 119 , 120 ]. Accordingly, stroke increased the level of circulating M-MDSCs in human stroke patients [ 121 ].…”

Systemic immune responses after ischemic stroke: From the center to the periphery

“…Th1 cells secrete proinflammatory cytokines and Th2 cells produce anti-inflammatory cytokines ( 87 ). It is important to note that Treg cells, which are identified by expression of transcription factor forkhead box (FOX)P3, play a beneficial role in stroke ( 88 , 89 ). Treg cells are rare in the early stages of the disease.…”

“…Promotion and maintenance of the anti-inflammatory phenotype of microglia is another important mechanism by which Treg cells play a neuroprotective role ( 92 ). Hence, Treg cells could be an effective target for the treatment of stroke in the future ( 89 ).…”