Identification of astrocyte-derived immune suppressor factor that induces apoptosis of autoreactive T cells

Hara, Hideo; Nanri, Yasuhiro; Tabata, Emi; Mitsutake, Saori; Tabira, Takeshi

doi:10.1016/j.jneuroim.2010.12.011

Cited by 17 publications

(12 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, astrocytes might be the cells that produce major collagen components of the fibrosis in MS [25], as they were shown to express these molecules in vitro [26]. As already mentioned, astrocytes induce apoptosis in T cells through generation of an ECM component osteonectin [18]. Thus, in these ways, astrocytes might contribute to the limitation of neuroinflammation in the CNS.…”

Section: Masons and Wreckersmentioning

confidence: 89%

Astrocytes in the tempest of multiple sclerosis

2011

View full text Add to dashboard Cite

Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity‐related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes.

show abstract

Section: Masons and Wreckersmentioning

confidence: 89%

Astrocytes in the tempest of multiple sclerosis

2011

View full text Add to dashboard Cite

show abstract

“…Both extrinsic and intrinsic pathways of apoptosis affect EAE development 46–49 . The death of oligodendrocytes not only causes direct demyelination but also releases “danger signals” which further induce sterile inflammation.…”

Section: Discussionmentioning

confidence: 99%

Act1 mediates IL-17–induced EAE pathogenesis selectively in NG2+ glial cells

et al. 2013

View full text Add to dashboard Cite

Interleukin 17(IL-17) is a signature cytokine of Th17 cells. We previously reported that deletion of NF-κ B activator 1(Act1), the key transducer of IL-17R signaling, from the neuroectodermal lineage in mice (neurons, oligodendrocytes, astrocytes)results in attenuated severity of experimental autoimmune encephalomyelitis (EAE). Here we examined the cellular basis of this observation. EAE disease course was unaffected by deleting Act1 from neurons or mature oligodendrocytes and Act1 deletion from astrocytes only modestly affected disease course. Deletion of Act1 from NG2+ glia resulted in markedly reduced EAE severity. Furthermore, IL-17 induced characteristic inflammatory mediator expression in NG2+ glial cells. Additionally, IL-17 also exhibited strong inhibitory effects on the maturation of oligodendrocyte lineage cells in vitro and reduced their survival. These data identify NG2+ glia as the major CNS cellular target of IL-17 in EAE. The sensitivity of oligodendrocyte lineage cells to IL-17-mediated toxicity further suggests a direct link between inflammation and neurodegeneration in multiple sclerosis (MS).

show abstract

“…In addition, conditioned medium from IFN-␥ stimulated astrocytes was shown to suppress T-cell proliferation and activation (38). More recently, it has been shown that IFN-␥ induces the expression of a protein termed astrocytederived immune-suppressor factor (AdiF), which can also promote apoptosis of T-cells (39). Finally, the idea that proinflammatory cytokine production can mitigate ongoing CNS inflammation is also more generally supported by the fact that mice deficient in IFN-␥ (40, 41) or IFN-␥ receptor (42) develop atypical EAE characterized by a more aggressive phenotype.…”

Section: Dissussionmentioning

confidence: 99%