Astroglial-derived lymphotoxin-alpha exacerbates inflammation and demyelination, but not remyelination

Glia
Sheila R PlantJenny P-Y Ting

Abstract

Tumor necrosis factoralpha (TNFalpha) and lymphotoxin-alpha (Ltalpha) are upregulated in and around multiple sclerosis plaques and are proposed to play a role during chronic inflammation in demyelinating disease. Despite the perceived detrimental role of these cytokines, human clinical trials inhibiting TNFalpha signaling has led to worsening of symptoms in multiple sclerosis (MS) patients. Our laboratory has verified a role for TNFalpha in the exacerbation of demyelination but, more importantly, has demonstrated a novel role for TNFalpha in reparative remyelination in a cuprizone-induced demyelination model. This may explain the worsening of symptoms experienced by MS patients. In view of the cross-talk in TNF family signaling, the aim of this study is to understand the role of Ltalpha in demyelination and remyelination in hopes of improving therapeutic strategies for MS. Using the same model, we show that mice lacking Ltalpha exhibit a delay in demyelination that is greater than that exhibited by TNFalpha null mice. In this model, Ltalpha is expressed primarily by astroglia. The delay in demyelination is accompanied by a delay in the loss of mature GSTpi-positive oligodendrocytes in Ltalpha-/- mice compared with wild-type mic...Continue Reading

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Citations

Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Krishnan Sriram, James P O'Callaghan
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Jul 27, 2021·Frontiers in Immunology·Fabian RichterRoman Fischer

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