Abstract
Regulatory T cells (Tregs) play an anti-inflammatory effect to protect against ischemic stroke. Plasmacytoid dendritic cells (pDCs) can induce regulatory T cells tolerance in sterile-inflammation conditions. However, whether and how pDCs-mediated Tregs response play a part in the pathology of ischemic stroke remains unclear. In this study, we showed that pDCs were increased in the brain of middle cerebral artery occlusion (MCAO) mice. Depletion of pDCs with 120G8 exacerbated MCAO-induced brain injury, peripheral pro-inflammation response and decreased the systemic Tregs in mice. Furthermore, the data of mixed lymphocyte reaction (MLR) in vitro demonstrate that splenic pDCs from MCAO mice can significantly promote Tregs proliferation, accompanying with the increased expression of indoleamine 2,3-dioxygenase 1 (IDO1) on pDCs. Taken together, the findings here suggested that under the pathologic state of stroke, pDCs protect against MCAO-induced brain injury by priming Tregs, illustrating that pDCs represented as a therapeutic target for the prevention of ischemic brain injury.
Highlights
Stroke is the leading cause of lethality and permanent disability throughout the world (Feigin, 2019)
In order to identify the effect of middle cerebral artery occlusion (MCAO) on the Plasmacytoid dendritic cells (pDCs), the brains, spleens and blood samples were collected at 2 days after MCAO, and pDCs were analyzed by flow cytometry
MCAO exerted minimal effects on the percentages of blood and splenic pDCs (0.82% vs. 0.94% in Figure 1C, 0.25% vs. 0.26% in Figure 1D, respectively). These results suggest that pDCs participate in the pathology of ischemic stroke-induced brain injury
Summary
Stroke is the leading cause of lethality and permanent disability throughout the world (Feigin, 2019). Recent studies demonstrate that immune response, especially mediated by T lymphocytes plays an important role in the pathology of stroke (Vidale et al, 2017; Shekhar et al, 2018; Nakamura and Shichita, 2019). Among T lymphocytes subsets, accumulating evidence indicates regulatory T cells (Tregs), which function to suppress excessive immune responses, play an anti-inflammatory effect to protect against ischemic stroke (Duffy et al, 2018). Previous studies have shown that adoptive Tregs therapy could ameliorate blood-brain barrier damage after cerebral ischemia and TPA-induced brain hemorrhage after stroke (Li et al, 2013; Li P. et al, 2017; Mao et al, 2017). How the Tregs were primed on the stroke progression has not been fully illustrated
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