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

Abstract

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.

Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats

“…The activated microglia/macrophages with rounded shape, voluminous cytoplasm, and abundant myelin debris are morphological characteristics of anti-inflammatory cells with high phagocytic activity (Wirjatijasa et al, 2002;Nakajima et al, 2012;Ishii et al, 2013). In the present study, the administration of MSCs favored the activation of microglia/macrophages with characteristic anti-inflammatory morphology and reduced the inflammatory infiltrate in the white and gray matter 8 days after spinal cord injury, which improved regeneration following injury.…”

Alleviation of spinal cord injury by Ginkgolide B via the inhibition of STAT1 expression

“…The protective role of Ginkgolide B in SCI has not been reported; therefore, we hypothesized that Ginkgolide B might exert its protection of the spinal cord through the STAT1 pathway. This is based on evidence showing the alteration of important transcription factors, such as STAT1 and tumor growth factor b (TGF-b), in other injured tissues such as bone (Han et al, 2012;Ishii et al, 2013). Thus, we hypothesized that Ginkgolide B might exert similar effects through STAT1 in SCI.…”

STAT1 inhibitor alleviates spinal cord injury by decreasing apoptosis

“…Physical injury is the most common reason underlying SCI and it results in both primary and secondary injuries, the latter of which include apoptosis of neuronal and glial cells, elevated permeability of the spinal cord barrier, and elongation of the neural reflex response (Ishii et al, 2013). The secondary inflammatory response in SCI is even more severe in the spinal cord than in cerebral damage.…”