Journal
CELL DEATH & DISEASE
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2013.234
Keywords
Th1 cells; spinal cord injury; microglia macrophages; interleukin 10
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Funding
- Japan Society for the Promotion of Science (JSPS)
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Transfer of type-1 helper T-gamma onditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-gamma (ifn-gamma) knockout mice (ifn-gamma(-/-) Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MUs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-gamma(-/-) Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-gamma-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10(-/-)) mice had no effects on recovery from SCI. These findings demonstrate that ifn-gamma-dependent secretion of IL-10 from Th1 cells, as well as native MG/MUs, is required for the promotion of motor recovery after SCI.
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