Regulatory T Cells in Post-stroke Immune Homeostasis

Abstract

The secondary neuroinflammatory response has come into focus of experimental stroke research. Immunological mechanisms after acute stroke are being investigated in the hope to identify novel and druggable pathways that contribute to secondary infarct growth after stroke. Among a variety of neuroimmunological events after acute brain ischemia, including microglial activation, brain leukocyte invasion, and secretion of pro-inflammatory factors, lymphocytes have been identified as the key leukocyte subpopulation driving the neuroinflammatory response and contributing to stroke outcome. Several studies have shown that pro-inflammatory lymphocyte subpopulations worsen stroke outcome and that inhibiting their invasion to the injured brain is neuroprotective. In contrast to the effector functions of pro-inflammatory lymphocytes, regulatory T cells (Treg) are critically involved in maintaining immune homeostasis and have been characterized as disease-limiting protective cells in several inflammatory conditions, particularly in primary inflammatory diseases of the central nervous system (CNS). However, due to the complex function of regulatory cells in immune homeostasis and disease, divergent findings have been described for the role of Treg in stroke models. Emerging evidence suggests that this discrepancy arises from potentially differing functions of Treg depending on the predominant site of action within the neurovascular unit and the surrounding inflammatory milieu. This article will provide a comprehensive review of current findings on Treg in brain ischemia models and discuss potential reasons for the observed discrepancies.

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Correspondence to Arthur Liesz.

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This work was supported the Excellence Cluster for Systems Neurology (SyNergy) and by grants from the German Research Foundation (DFG), project LI2534/1-1 to A.L. and SFB 688, project A13 and KL2323/6-1 to C.K.

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Liesz, A., Kleinschnitz, C. Regulatory T Cells in Post-stroke Immune Homeostasis. Transl. Stroke Res. 7, 313–321 (2016). https://doi.org/10.1007/s12975-016-0465-7

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Keywords

  • Stroke
  • Animal models
  • Regulatory T cell
  • Immunity
  • Inflammation