Regulatory T cells in ischemic stroke

Abstract

The pathophysiological mechanisms of neuroinflammation, angiogenesis, and neuroplasticity are currently the hotspots of researches in ischemic stroke. Regulatory T cells (Tregs), a subset of T cells that control inflammatory and immune responses in the body, are closely related to the pathogenesis of ischemic stroke. They participate in the inflammatory response and neuroplasticity process of ischemic stroke by various mechanisms, such as secretion of anti‐inflammatory factors, inhibition of pro‐inflammatory factors, induction of cell lysis, production of the factors that promote neural regeneration, and modulation of microglial and macrophage polarization. However, it remains unclear whether Tregs play a beneficial or deleterious role in ischemic stroke and the effect of Tregs in different stages of ischemic stroke. Here, we discuss the dynamic changes of Tregs at various stages of experimental and clinical stroke, the potential mechanisms under Tregs in regulating stroke and the preclinical studies of Tregs‐related treatments, in order to provide a reference for clinical treatment.

Neuroinflammation in Cerebral Ischemia and Ischemia/Reperfusion Injuries: From Pathophysiology to Therapeutic Strategies

“…Lymphocytes have less important contributions in cerebral ischemic injury; the mechanisms are mainly related to the innate T cell functions [ 103 ]. IL-17 secreting γδT cells, CD4 + T cells, and CD8 + T cells may infiltrate the parenchyma within hours after stroke onset, peak by day 3, and aggravate ischemic injury [ 68 , 103 , 104 ], as do natural killer T cells [ 105 ], while regulatory lymphocytes (Tregs) expressing the forkhead box P3 (Foxp3) transcription factor [ 106 , 107 ] have traditionally been regarded as exhibiting neuroprotective activity [ 108 , 109 ]. The choroid plexuses appear to be the preferential route for infiltration by lymphocytes since in an experimental setting, infarction of the choroid plexus resulted in diminished lymphocyte infiltration [ 110 ].…”

Microglia: The Hub of Intercellular Communication in Ischemic Stroke

“…Contrary, Kleinschnitz et al ( 2013 ) found a marked increase of Foxp3 + Tregs in the brain within 24 h after tMCAO, but predominantly in the cerebral vasculature. Tregs play a double-edged role in IS, but primarily with a neuroprotective effect (Wang H. et al, 2021 ). Brain Tregs can modulate the microglia/macrophages polarization toward M2-type in cerebral ischemia by secreting IL-10 and TGF-β, therefore protecting against secondary brain damage (Liesz et al, 2009 ; Liu et al, 2011 ).…”

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 ].…”