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Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation

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Item Type:Article
Title:Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation
Creators Name:Starossom, S.C. and Campo Garcia, J. and Woelfle, T. and Romero-Suarez, S. and Olah, M. and Watanabe, F. and Cao, L. and Yeste, A. and Tukker, J.J. and Quintana, F.J. and Imitola, J. and Witzel, F. and Schmitz, D. and Morkel, M. and Paul, F. and Infante-Duarte, C. and Khoury, S.J.
Abstract:In demyelinating diseases including multiple sclerosis (MS), neural stem cells (NSCs) can replace damaged oligodendrocytes if the local microenvironment supports the required differentiation process. Although chitinase-like proteins (CLPs) form part of this microenvironment, their function in this differentiation process is unknown. Here, we demonstrate that murine Chitinase 3-like-3 (Chi3l3/Ym1), human Chi3L1 and Chit1 induce oligodendrogenesis. In mice, Chi3l3 is highly expressed in the subventricular zone, a stem cell niche of the adult brain, and in inflammatory brain lesions during experimental autoimmune encephalomyelitis (EAE). We find that silencing Chi3l3 increases severity of EAE. We present evidence that in NSCs Chi3l3 activates the epidermal growth factor receptor (EGFR), thereby inducing Pyk2-and Erk1/2- dependent expression of a pro-oligodendrogenic transcription factor signature. Our results implicate CLP-EGFR-Pyk2-MEK-ERK as a key intrinsic pathway controlling oligodendrogenesis.
Keywords:Chitinase-3-Like Protein 1, Experimental, Autoimmune, Encephalomyelitis, ErbB Receptors, HEK293 Cells, Hexosaminidases, Lectins, MAP Kinase Signaling System, Neural Stem Cells, Oligodendroglia, Beta-N-Acetylhexosaminidases, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:217
Date:15 January 2019
Official Publication:https://doi.org/10.1038/s41467-018-08140-7
PubMed:View item in PubMed

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