Imbalance between IL-17A-Producing Cells and Regulatory T Cells during Ischemic Stroke

Abstract

Immune responses and inflammation are key elements in the pathogenesis of ischemic stroke (IS). Although the involvement of IL-17A in IS has been demonstrated using animal models, the involvement of IL-17A and IL-17-secreting T cell subsets in IS patients has not been verified, and whether the balance of Treg/IL-17-secreting T cells is altered in IS patients remains unknown. In the present study, we demonstrated that the proportion of peripheral Tregs and the levels of IL-10 and TGF-β were reduced in patients with IS compared with controls using flow cytometry (FCM), real-time PCR, and ELISA assays. However, the proportions of Th17 and γ δ T cells, the primary IL-17A-secreting cells, increased dramatically, and these effects were accompanied by increases in the levels of IL-17A, IL-23, IL-6, and IL-1β in IS patients. These studies suggest that the increase in IL-17A-producing cells and decrease in Treg cells might contribute to the pathogenesis of IS. Manipulating the balance between Tregs and IL-17A-producing cells might be helpful for the treatment of IS.

Increased frequency of circulating regulatory T cells in patients with acute cerebral hemorrhage

“…In humans, Tregs are elevated in the peripheral blood of patients on days 7 and 21 after acute ischemic stroke, suggesting that such adaptive changes are possibly related to their protective action against stroke-induced damages [22]. However, in contrast to these neuroprotective effects on stroke, a recent study indicates that the proportion of peripheral Tregs and the levels of IL-10 and TGF-␤ were significantly reduced along with the elevation of circulatory IL-17A-producing cells in patients at days 7 and 28 after ischemic stroke compared to controls [9]. Another study indicated that Foxp3 + Treg-depletion did not affect the infarct volume in MCAO mice [18].…”

“…Adoptive Tregs therapy can reduce infarct size, promote tissue repair, down-regulate deleterious pro-inflammatory cytokines and alleviate the dysfunction of ischemic stroke models [14]. Cytokines TGF-␤ and IL-10 were reported to have antiinflammatory and neuroprotective roles in ischemic stroke [9,21]. In humans, Tregs are elevated in the peripheral blood of patients on days 7 and 21 after acute ischemic stroke, suggesting that such adaptive changes are possibly related to their protective action against stroke-induced damages [22].…”

“…These injuries result in neural dysfunctions caused by cerebral edema, neuronal apoptosis, degeneration and necrosis that eventuhttp://dx.doi.org/10.1016/j.neulet.2015.02.042 0304-3940/© 2015 Elsevier Ireland Ltd. All rights reserved. ally interrupt of neural circuity [1,5,9,23,24]. Altered immune status and time-dependent recruitment of different inflammatory cells imply that most of the inflammatory cell types display beneficial and/or adverse effects following ICH.…”

Mechanisms of poststroke fatigue

“…The evidence in favour of such a mechanism in PSF is still weak. One study in particular reported reduced percentage of circulating regulatory T cells combined with increased systemic Th17 and proinflammatory cytokines and reduced anti-inflammatory cytokines 94. In addition, interferon-gamma, the cytokine primarily responsible for upregulating IDO, was not higher in stroke81 when compared with healthy controls.…”

Inflammatory Signaling in Post-Stroke Fatigue and Depression

“…The disrupted balance between these 2 CD4+ T cell subsets, namely, an excess of pro-inflammatory Th17 cells relative to anti-inflammatory Treg cells, has been implicated in chronic inflammation and autoimmunity [72]. Preliminary evidence of an altered Th17/Treg balance in stroke was recently demonstrated [73]. Brain inflammation alters the functioning of hypothalamic orexin-secreting neurons and decreases the synthesis and activity of monoamine neurotransmitters (Fig.…”