Abstract
Signaling by the mammalian target of rapamycin (mTOR) plays an important role in the modulation of both innate and adaptive immune responses. However, the role and underlying mechanism of mTOR signaling in poststroke neuroinflammation are largely unexplored. In this study, we injected rapamycin, a mTOR inhibitor, by the intracerebroventricular route 6 h after focal ischemic stroke in rats.We found that rapamycin significantly reduced lesion volume and improved behavioral deficits. Notably, infiltration of γδ T cells and granulocytes, which are detrimental to the ischemic brain, was profoundly reduced after rapamycin treatment, as was the production of proinflammatory cytokines and chemokines by macrophages and microglia. Rapamycin treatment prevented brain macrophage polarization toward the M1 type. In addition, we also found that rapamycin significantly enhanced antiinflammation activity of regulatory T cells (Tregs), which decreased production of proinflammatory cytokines and chemokines by macrophages and microglia. Depletion of Tregs partially elevated macrophage/microglia-induced neuroinflammation after stroke. Our data suggest that rapamycin can attenuate secondary injury and motor deficits after focal ischemia by enhancing the antiinflammation activity of Tregs to restrain poststroke neuroinflammation.
| Original language | English |
|---|---|
| Pages (from-to) | 6009-6019 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 192 |
| Issue number | 12 |
| DOIs | |
| State | Published - 15 Jun 2014 |
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MTOR Signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia. / Xie, Luokun; Sun, Fen; Wang, Jixian; Mao, Xiao Ou; Xie, Lin; Yang, Shaohua; Su, Dong Ming; Simpkins, James W.; Greenberg, David A.; Jin, Kunlin.
In: Journal of Immunology, Vol. 192, No. 12, 15.06.2014, p. 6009-6019.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - MTOR Signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia
AU - Xie, Luokun
AU - Sun, Fen
AU - Wang, Jixian
AU - Mao, Xiao Ou
AU - Xie, Lin
AU - Yang, Shaohua
AU - Su, Dong Ming
AU - Simpkins, James W.
AU - Greenberg, David A.
AU - Jin, Kunlin
PY - 2014/6/15
Y1 - 2014/6/15
N2 - Signaling by the mammalian target of rapamycin (mTOR) plays an important role in the modulation of both innate and adaptive immune responses. However, the role and underlying mechanism of mTOR signaling in poststroke neuroinflammation are largely unexplored. In this study, we injected rapamycin, a mTOR inhibitor, by the intracerebroventricular route 6 h after focal ischemic stroke in rats.We found that rapamycin significantly reduced lesion volume and improved behavioral deficits. Notably, infiltration of γδ T cells and granulocytes, which are detrimental to the ischemic brain, was profoundly reduced after rapamycin treatment, as was the production of proinflammatory cytokines and chemokines by macrophages and microglia. Rapamycin treatment prevented brain macrophage polarization toward the M1 type. In addition, we also found that rapamycin significantly enhanced antiinflammation activity of regulatory T cells (Tregs), which decreased production of proinflammatory cytokines and chemokines by macrophages and microglia. Depletion of Tregs partially elevated macrophage/microglia-induced neuroinflammation after stroke. Our data suggest that rapamycin can attenuate secondary injury and motor deficits after focal ischemia by enhancing the antiinflammation activity of Tregs to restrain poststroke neuroinflammation.
AB - Signaling by the mammalian target of rapamycin (mTOR) plays an important role in the modulation of both innate and adaptive immune responses. However, the role and underlying mechanism of mTOR signaling in poststroke neuroinflammation are largely unexplored. In this study, we injected rapamycin, a mTOR inhibitor, by the intracerebroventricular route 6 h after focal ischemic stroke in rats.We found that rapamycin significantly reduced lesion volume and improved behavioral deficits. Notably, infiltration of γδ T cells and granulocytes, which are detrimental to the ischemic brain, was profoundly reduced after rapamycin treatment, as was the production of proinflammatory cytokines and chemokines by macrophages and microglia. Rapamycin treatment prevented brain macrophage polarization toward the M1 type. In addition, we also found that rapamycin significantly enhanced antiinflammation activity of regulatory T cells (Tregs), which decreased production of proinflammatory cytokines and chemokines by macrophages and microglia. Depletion of Tregs partially elevated macrophage/microglia-induced neuroinflammation after stroke. Our data suggest that rapamycin can attenuate secondary injury and motor deficits after focal ischemia by enhancing the antiinflammation activity of Tregs to restrain poststroke neuroinflammation.
UR - http://www.scopus.com/inward/record.url?scp=84902203576&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1303492
DO - 10.4049/jimmunol.1303492
M3 - Article
VL - 192
SP - 6009
EP - 6019
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -