ifn-γ-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury

被引：0
作者：
H Ishii
S Tanabe
M Ueno
T Kubo
H Kayama
S Serada
M Fujimoto
K Takeda
T Naka
T Yamashita
机构：
[1] Graduate School of Medicine,Department of Molecular Neuroscience
[2] Osaka University,Department of Neurobiology
[3] 2-2 Yamadaoka,Department of Microbiology and Immunology
[4] Osaka 565-0871,undefined
[5] Japan,undefined
[6] JST,undefined
[7] CREST,undefined
[8] 5 Sanbancho,undefined
[9] Graduate School of Medicine,undefined
[10] Chiba University,undefined
[11] 1-8-1 Inohana,undefined
[12] Chiba 260-8677,undefined
[13] Japan,undefined
[14] Laboratory of Mucosal Immunology,undefined
[15] Graduate School of Medicine,undefined
[16] Osaka University,undefined
[17] 2-2 Yamadaoka,undefined
[18] Osaka 565-0871,undefined
[19] Japan,undefined
[20] WPI Immunology Frontier Research Center,undefined
[21] Osaka University,undefined
[22] 2-2 Yamadaoka,undefined
[23] Osaka 565-0871,undefined
[24] Japan,undefined
[25] Laboratory for Immune Signal,undefined
[26] National Institute of Biomedical Innovation,undefined
[27] 7-6-8 Saito-Asagi,undefined
[28] Osaka 565-0085,undefined
[29] Japan,undefined
来源：
Cell Death & Disease | 2013年 / 4卷
关键词：
Th1 cells; spinal cord injury; microglia macrophages; interleukin 10;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Transfer of type-1 helper T-conditioned (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-γ (ifn-γ) knockout mice (ifn-γ−/− Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ−/− 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-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10−/−) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI.
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页码：e710 / e710
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[1]  
David S(1981)Axonal elongation into peripheral nervous system ‘bridges’ after central nervous system injury in adult rats Science 214 931-933
[2]  
Aguayo AJ(2007)Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration Exp Neurol 204 220-233
[3]  
Bye N(2010)Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment Brain 133 433-447
[4]  
Habgood MD(2008)Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury Exp Neurol 209 378-388
[5]  
Callaway JK(2006)Augmented locomotor recovery after spinal cord injury in the athymic nude rat J Neurotrauma 23 660-673
[6]  
Malakooti N(2009)Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury Nat Med 15 946-950
[7]  
Potter A(2003)Autoreactive T cells promote post-traumatic healing in the central nervous system J Neuroimmunol 134 25-34
[8]  
Kossmann T(2006)Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood Nat Neurosci 9 268-275
[9]  
Beck KD(2008)T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS Proc Natl Acad Sci USA 105 17913-17918
[10]  
Nguyen HX(2012)Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and functional recovery after spinal cord injury Cell Death Dis 3 e363-112
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